COVID-19-associated lymphopenia: Difference between revisions

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{{Main|COVID-19}}
'''For COVID-19 frequently asked inpatient questions, click [[COVID-19 frequently asked inpatient questions|here]]'''<br>
'''For COVID-19 frequently asked inpatient questions, click [[COVID-19 frequently asked inpatient questions|here]]'''<br>
'''For COVID-19 frequently asked outpatient questions, click [[COVID-19 frequently asked outpatient questions|here]]'''<br>
'''For COVID-19 frequently asked outpatient questions, click [[COVID-19 frequently asked outpatient questions|here]]'''<br>
{{SI}}
{{SI}}


{{CMG}}; {{AE}} [[User:Fausatadogba|Oluwabusola Fausat Adogba, MD]]
{{CMG}}; {{AE}} {{FOA}}


{{SK}}  
{{SK}}Lymphocyte changes in COVID-19, sars-cov-2 related lymphopenia


==Overview==
==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]].
[[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]] in covid19 infection are direct infection of [[lymphocyte]], direct destroying of [[lymphocytic]] organs, inflammatory [[Cytokine|cytokines]] such as [[TNF-α|TNFɑ]], [[Interleukin 6|IL-6]], [[lymphocyte]] inhibition.  


==Historical Perspective==
==Historical Perspective==
*[[Coronavirus]] disease 2019 ([[COVID-19]]) has been considered as a global [[pandemic]] since its first emergence in Wuhan,China.<ref name="urlWHO Western Pacific | World Health Organization">{{cite web |url=https://www.who.int/westernpacific/emergencies/covid-19 |title=WHO Western Pacific &#124; World Health Organization |format= |work= |accessdate=}}</ref>
* 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.<ref name="RuanYang2020">{{cite journal|last1=Ruan|first1=Qiurong|last2=Yang|first2=Kun|last3=Wang|first3=Wenxia|last4=Jiang|first4=Lingyu|last5=Song|first5=Jianxin|title=Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China|journal=Intensive Care Medicine|volume=46|issue=5|year=2020|pages=846–848|issn=0342-4642|doi=10.1007/s00134-020-05991-x}}</ref>


*[[Coronavirus]] disease 2019 (COVID-19) has been considered as a global [[pandemic]] since its first emergence in Wuhan,China.<ref name="urlWHO Western Pacific | World Health Organization">{{cite web |url=https://www.who.int/westernpacific/emergencies/covid-19 |title=WHO Western Pacific &#124; World Health Organization |format= |work= |accessdate=}}</ref>
==Classification==
*There is no established system for the classification regarding COVID-19 related [[lymphopenia]].


* On March 12, 2020, the [[World Health Organization]] declared the COVID-19 outbreak a pandemic.
==Pathophysiology==
* Since the first descriptive study lymphocyte count has been a marker of interest.<ref name="RuanYang2020">{{cite journal|last1=Ruan|first1=Qiurong|last2=Yang|first2=Kun|last3=Wang|first3=Wenxia|last4=Jiang|first4=Lingyu|last5=Song|first5=Jianxin|title=Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China|journal=Intensive Care Medicine|volume=46|issue=5|year=2020|pages=846–848|issn=0342-4642|doi=10.1007/s00134-020-05991-x}}</ref>
*There are four hypothetical mechanisms regarding [[lymphopenia]]:<ref name="FischerHoffmann2007">{{cite journal|last1=Fischer|first1=Karin|last2=Hoffmann|first2=Petra|last3=Voelkl|first3=Simon|last4=Meidenbauer|first4=Norbert|last5=Ammer|first5=Julia|last6=Edinger|first6=Matthias|last7=Gottfried|first7=Eva|last8=Schwarz|first8=Sabine|last9=Rothe|first9=Gregor|last10=Hoves|first10=Sabine|last11=Renner|first11=Kathrin|last12=Timischl|first12=Birgit|last13=Mackensen|first13=Andreas|last14=Kunz-Schughart|first14=Leoni|last15=Andreesen|first15=Reinhard|last16=Krause|first16=Stefan W.|last17=Kreutz|first17=Marina|title=Inhibitory effect of tumor cell–derived lactic acid on human T cells|journal=Blood|volume=109|issue=9|year=2007|pages=3812–3819|issn=0006-4971|doi=10.1182/blood-2006-07-035972}}</ref><ref name="LiaoLiang2002">{{cite journal|last1=Liao|first1=Yuan-Chun|last2=Liang|first2=Wei-Guang|last3=Chen|first3=Feng-Wei|last4=Hsu|first4=Ju-Hui|last5=Yang|first5=Jiann-Jou|last6=Chang|first6=Ming-Shi|title=IL-19 Induces Production of IL-6 and TNF-α and Results in Cell Apoptosis Through TNF-α|journal=The Journal of Immunology|volume=169|issue=8|year=2002|pages=4288–4297|issn=0022-1767|doi=10.4049/jimmunol.169.8.4288}}</ref>
 
** Direct [[infection]] of [[lymphocytes]]
==Classification==
**Direct destroying [[Lymphatic system|lymphatic]] organs
There is no established system for the classification regarding COVID-19 related [[lymphopenia]].
**[[Inflammatory]] [[cytokines]] such as [[TNF-α|TNF-ɑ]], [[Interleukin 6|IL-6]], etc inducing [[lymphopenia]]
**Inhibition of [[lymphocytes]] by [[metabolic]] [[molecules]] such as hyperlactic [[acidemia]]


==Causes==
==Causes==
 
*The [[SARS-CoV-2]] ([[COVID-19]]) viral [[infection]] is the known cause of [[lymphopenia]] in [[COVID-19]] patients. To read more click [[COVID-19|here]]
*There are four hypothetical mechanisms regardin lymphopenia:<ref name="FischerHoffmann2007">{{cite journal|last1=Fischer|first1=Karin|last2=Hoffmann|first2=Petra|last3=Voelkl|first3=Simon|last4=Meidenbauer|first4=Norbert|last5=Ammer|first5=Julia|last6=Edinger|first6=Matthias|last7=Gottfried|first7=Eva|last8=Schwarz|first8=Sabine|last9=Rothe|first9=Gregor|last10=Hoves|first10=Sabine|last11=Renner|first11=Kathrin|last12=Timischl|first12=Birgit|last13=Mackensen|first13=Andreas|last14=Kunz-Schughart|first14=Leoni|last15=Andreesen|first15=Reinhard|last16=Krause|first16=Stefan W.|last17=Kreutz|first17=Marina|title=Inhibitory effect of tumor cell–derived lactic acid on human T cells|journal=Blood|volume=109|issue=9|year=2007|pages=3812–3819|issn=0006-4971|doi=10.1182/blood-2006-07-035972}}</ref><ref name="LiaoLiang2002">{{cite journal|last1=Liao|first1=Yuan-Chun|last2=Liang|first2=Wei-Guang|last3=Chen|first3=Feng-Wei|last4=Hsu|first4=Ju-Hui|last5=Yang|first5=Jiann-Jou|last6=Chang|first6=Ming-Shi|title=IL-19 Induces Production of IL-6 and TNF-α and Results in Cell Apoptosis Through TNF-α|journal=The Journal of Immunology|volume=169|issue=8|year=2002|pages=4288–4297|issn=0022-1767|doi=10.4049/jimmunol.169.8.4288}}</ref>
** Direct infection of [[Lymphocyte|Lymphocytes]]
**Direct destroying [[Lymphatic system|lymphatic]] organs
**[[Inflammatory]] [[cytokines]] such as TNF ἀ, IL-6 , etc inducing [[lymphopenia]]
**Inhibition of [[lymphocytes]] by [[metabolic]] [[molecules]] such as hyperlactic [[acidemia]]


==Differentiating COVID-19 related  Lymphocytopenia from other Diseases==
==Differentiating COVID-19 related  Lymphocytopenia from other Diseases==
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]],<ref name="">{{cite journal | author=W L Ng, C M Chu, A K L Wu, V C C Cheng, K Y Yuen | title=Lymphopenia at presentation is associated with increased risk of infections in patients with systemic lupus erythematosus | journal=Quarterly Journal of Medicine | volume= 99 | issue=1 | pages=37-47 | doi=10.1093/qjmed/hci155}}</ref> high [[stress (medicine)|stress]] levels, whole body radiation, [[rheumatoid arthritis]], and [[iatrogenic]] conditions.
* [[Lymphocytopenia]], is associated and must be differentiated from the following diseases which includes the following:<ref name="">{{cite journal | author=W L Ng, C M Chu, A K L Wu, V C C Cheng, K Y Yuen | title=Lymphopenia at presentation is associated with increased risk of infections in patients with systemic lupus erythematosus | journal=Quarterly Journal of Medicine | volume= 99 | issue=1 | pages=37-47 | doi=10.1093/qjmed/hci155}}</ref><ref>Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:77 ISBN 1591032016</ref><ref>Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:68 ISBN 140510368X</ref>
 
**After [[influenza]]
In alphabetical order. <ref>Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:77 ISBN 1591032016</ref> <ref>Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:68 ISBN 140510368X</ref>
**After [[Snakebites|snakebite]]
 
**[[Anesthesia]]
*After [[influenza]]
** Antibody deficiency syndrome
*After [[Snakebites|snakebite]]
**[[Aplastic Anemia]]
*[[Anesthesia]]
**[[Banti's Syndrome]]
* Antibody deficiency syndrome
**[[Burns]]
*[[Aplastic Anemia]]
**Congenital immune deficiency
*[[Banti's Syndrome]]
**[[Cushing's Disease]]
*[[Burns]]
**[[Dermatomyositis]]
*Congenital immune deficiency
**[[Drugs]], toxins
*[[Cushing's Disease]]
**[[Exudative enteropathy]]
*[[Dermatomyositis]]
**[[Felty's Syndrome]]
*[[Drugs]], toxins
**Heavy [[exercise]]
*[[Exudative enteropathy]]
**[[HIV]]
*[[Felty's Syndrome]]
**[[Hodgkin's Lymphoma]]
*Heavy [[exercise]]
**[[Inflammatory Bowel Disease]]
*[[HIV]]
**[[Lymphocyte]] [[tuberculosis]]
*[[Hodgkin's Lymphoma]]
**[[Measles]]
*[[Inflammatory Bowel Disease]]
**[[Paroxysmal nocturnal hemoglobinuria]]
*Lymphocyte [[tuberculosis]]
**[[Polycythemia]]
*[[Measles]]
**Postoperative
*[[Paroxysmal nocturnal hemoglobinuria]]
**[[Pregnancy]]
*[[Polycythemia]]
**[[Sarcoidosis]]
*Postoperative
**[[Scarlet Fever]]
*[[Pregnancy]]
**Secondary [[hypersplenism]]
*[[Sarcoidosis]]
**Single [[Non-Hodgkin lymphoma|non-Hodgkin's lymphomas]]
*[[Scarlet Fever]]
**[[Surgery]]
*Secondary [[hypersplenism]]
**[[Systemic Lupus Erythematosus]]
*Single non-Hodgkin's [[lymphoma]]s
**[[Trauma]]
*[[Surgery]]
**[[Tuberculosis]]
*[[Systemic Lupus Erythematosus]]
**[[Uremia]]
*[[Trauma]]
**[[Whipple's Disease]]
*[[Tuberculosis]]
**[[Zinc deficiency]]
*[[Uremia]]
*[[Whipple's Disease]]
*[[Zinc deficiency]]


==Epidemiology and Demographics==
==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.<ref name="urlWHO Coronavirus Disease (COVID-19) Dashboard | WHO Coronavirus Disease (COVID-19) Dashboard">{{cite web |url=https://covid19.who.int/?gclid=CjwKCAjw_-D3BRBIEiwAjVMy7NXI2vvO5rNBN-3aUwE4Lr3kcrhDJfoUkdlwlXtHXmTBoXBgseCGxRoCGpsQAvD_BwE |title=WHO Coronavirus Disease (COVID-19) Dashboard &#124; WHO Coronavirus Disease (COVID-19) Dashboard |format= |work= |accessdate=}}</ref> 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.
*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.<ref name="urlWHO Coronavirus Disease (COVID-19) Dashboard | WHO Coronavirus Disease (COVID-19) Dashboard">{{cite web |url=https://covid19.who.int/?gclid=CjwKCAjw_-D3BRBIEiwAjVMy7NXI2vvO5rNBN-3aUwE4Lr3kcrhDJfoUkdlwlXtHXmTBoXBgseCGxRoCGpsQAvD_BwE |title=WHO Coronavirus Disease (COVID-19) Dashboard &#124; WHO Coronavirus Disease (COVID-19) Dashboard |format= |work= |accessdate=}}</ref>
*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==
==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:<ref name="urlPeople Who Are at Higher Risk for Severe Illness | Coronavirus | COVID-19 | CDC">{{cite web |url=https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fneed-extra-precautions%2Fgroups-at-higher-risk.html |title=People Who Are at Higher Risk for Severe Illness &#124; Coronavirus &#124; COVID-19 &#124; CDC |format= |work= |accessdate=}}</ref>
 
*[[Chronic kidney disease]]  
* People of any age with certain underlying medical conditions are at increased risk for severe illness from [[COVID-19]]. These medical conditions include:<ref name="urlPeople Who Are at Higher Risk for Severe Illness | Coronavirus | COVID-19 | CDC">{{cite web |url=https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fneed-extra-precautions%2Fgroups-at-higher-risk.html |title=People Who Are at Higher Risk for Severe Illness &#124; Coronavirus &#124; COVID-19 &#124; CDC |format= |work= |accessdate=}}</ref>
*[[Chronic obstructive pulmonary disease]]
**[[Chronic kidney disease]]
*Immunocompromised state (weakened immune system) from solid organ transplant
**[[Chronic obstructive pulmonary disease]]
*Obesity (body mass index [BMI] of 30 or higher)
**[[Immunocompromised]] state (weakened [[immune system]]) from solid [[organ transplant]]
*Serious heart conditions, such as [[heart failure]], [[coronary artery disease]], or [[cardiomyopathies]]
**<nowiki/>[[Obesity]] (body mass index [<nowiki/>[[Body mass index|BMI]]] of 30 or higher)
*[[Sickle cell disease]]
**Serious [[Heart condition|heart conditions]], <nowiki/>such as [[heart failure]], [[coronary artery disease]], or [[cardiomyopathies]]
*[[Type 2 diabetes mellitus]]
**[[Sickle cell disease]]
**[[Type 2 diabetes mellitus]]


==Screening==
==Screening==
The Centers for Disease Control [[CDC]] has developed a laboratory test to help estimate how many people in the United States have been infected with SARS-CoV-2. This is known as the  [[serology]] test, and many commercial laboratories call it an antibody test. CDC is using this serologic (antibody) test to evaluate the performance of commercial antibody tests. [[CDC]] will develop guidance for the use of antibody tests in clinical and public health settings.
*[[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.<ref name="ZhaoMeng2020">{{cite journal|last1=Zhao|first1=Qianwen|last2=Meng|first2=Meng|last3=Kumar|first3=Rahul|last4=Wu|first4=Yinlian|last5=Huang|first5=Jiaofeng|last6=Deng|first6=Yunlei|last7=Weng|first7=Zhiyuan|last8=Yang|first8=Li|title=Lymphopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A systemic review and meta-analysis|journal=International Journal of Infectious Diseases|volume=96|year=2020|pages=131–135|issn=12019712|doi=10.1016/j.ijid.2020.04.086}}</ref>
An antibody test looks for the presence of antibodies, which are specific proteins made in response to infections. Antibodies are detected in the blood of people who are tested after infection; they show an immune response to the infection. Antibody test results are especially important for detecting previous infections in people who had few or no symptoms.
*A routine [[complete blood count]] ([[Complete blood count|CBC]]) with differential can be used for monitoring and predicting disease progression and severity in patients.


==Natural History, Complications, and Prognosis==
==Natural History, Complications, and Prognosis==
Common hematologic complications of [[coronavirus]] include [[lymphopenia]], [[COVID-19-associated neutrophilia|neutrophilia]] and [[COVID-19-associated thrombocytopenia|thrombocytosis]].
*[[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 &#124; CDC |format= |work= |accessdate=}}</ref>
[[Lymphopenia]] is a prominent part of severe COVID-19 and a [[lymphocyte]] count of less than 1.5 × 109/L may be useful in predicting the severity of clinical outcomes.<ref name="ZhaoMeng2020">{{cite journal|last1=Zhao|first1=Qianwen|last2=Meng|first2=Meng|last3=Kumar|first3=Rahul|last4=Wu|first4=Yinlian|last5=Huang|first5=Jiaofeng|last6=Deng|first6=Yunlei|last7=Weng|first7=Zhiyuan|last8=Yang|first8=Li|title=Lymphopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A systemic review and meta-analysis|journal=International Journal of Infectious Diseases|volume=96|year=2020|pages=131–135|issn=12019712|doi=10.1016/j.ijid.2020.04.086}}</ref>
*[[COVID-19]] related [[lymphocytopenia]] starts acutely in the course of the disease, with other manifestations of the disease.
*[[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 [[Prognosis|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>
*Common [[hematologic]] [[Complication (medicine)|complications]] of [[coronavirus]] also include [[COVID-19-associated neutrophilia|neutrophilia]] and [[COVID-19-associated thrombocytopenia|thrombocytosis]].


==Diagnosis==
==Diagnosis==
===Diagnostic Study of Choice===
===Diagnostic Choice of Study===
The primary method for diagnosis of COVID-19 is:
 
*Nuclei acid testing
* [[Lymphopenia]] refers to a count of less than 1,000 [[lymphocytes]] per micro liter of [[blood]] in adults, or less than 3,000 [[Lymphocyte|lymphocytes]] per microliter of blood in children. The following tests are used to diagnose [[lymphopenia]]:
Other tests include:
**[[Complete blood count]] ([[CBC]])
*Protein testing
**[[Flow cytometry]]
*[[CT scans]]


===History and Symptoms===
===History and 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 [[Coronavirus|virus]]. People with these symptoms may have COVID-19:
*[[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]]


==Lymphopenia as an indicator for severe disease==
* [[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 [[Coronavirus|virus]]. People with these symptoms may have [[COVID-19]]:<ref name="urlSymptoms of Coronavirus | CDC">{{cite web |url=https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html |title=Symptoms of Coronavirus &#124; 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. 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>
**[[Fever]] or [[chills]]
==References==  
**[[Cough]]
**[[Shortness of breath]] or [[Dyspnea|difficulty breathing]]
**[[Fatigue]]
**[[Muscle]] or [[body aches]]
**[[COVID-19-associated headache|Headache]]
**[[COVID-19-associated anosmia|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.
*For more information about [[COVID-19]] physical examination please click [[COVID-19 physical examination|here]].
 
===Laboratory findings===
*[[Lymphocyte]] count on [[Complete blood count|CBC]] with differential is less than 1.5x109/L is potentially associated with severe outcomes.<ref name="ZhaoMeng2020">{{cite journal|last1=Zhao|first1=Qianwen|last2=Meng|first2=Meng|last3=Kumar|first3=Rahul|last4=Wu|first4=Yinlian|last5=Huang|first5=Jiaofeng|last6=Deng|first6=Yunlei|last7=Weng|first7=Zhiyuan|last8=Yang|first8=Li|title=Lymphopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A systemic review and meta-analysis|journal=International Journal of Infectious Diseases|volume=96|year=2020|pages=131–135|issn=12019712|doi=10.1016/j.ijid.2020.04.086}}</ref>
*[[Peripheral blood smear]]- This maybe helpful, however there is insufficient evidence recommending routine [[peripheral blood smear]] in [[COVID-19]] patients.
*For more information about [[COVID-19]] laboratory findings please click [[COVID-19 laboratory findings|here]].
 
===Electrocardiogram===
* There are no [[The electrocardiogram|ECG]] findings associated with [[COVID-19]] associated [[Lymphocytopenia|lymphopenia]].
* To view the [[electrocardiogram]] findings on COVID-19, [[COVID-19 electrocardiogram|click here]].
 
===X-ray===
* There are no [[X-ray]] findings associated with [[COVID-19]] associated [[Lymphocytopenia|lymphopenia]].
* To view [[X-ray]] findings of COVID-19 ,click [[COVID-19 x ray|here]].
 
===Echocardiography or Ultrasound===
* There are no [[echocardiography]] or ultrasound findings associated with [[COVID-19]] associated [[Lymphocytopenia|lymphopenia]].
* To view the [[Echocardiography|echocardiographic]] findings on COVID-19, [[COVID-19 echocardiography and ultrasound|click here]].
 
===CT Scan===
* There are no [[Computed tomography|CT]] scan findings associated with [[COVID-19]] associated [[Lymphocytopenia|lymphopenia]].
* To view the [[Computed tomography|CT]] scan findings on COVID-19, [[COVID-19 CT scan|click here]].
 
===MRI===
* There are no [[Magnetic resonance imaging|MRI]] findings associated with [[COVID-19]] associated [[Lymphocytopenia|lymphopenia]].
* To view the [[Magnetic resonance imaging|MRI]] findings on COVID-19, [[COVID-19 MRI|click here]].
 
===Other imaging findings===
* There are no other imaging findings associated with [[COVID-19]] associated [[Lymphocytopenia|lymphopenia]].
* To view other imaging findings on COVID-19, [[COVID-19 other imaging findings|click here]].
 
===Other Diagnostic studies===
*[[Bone marrow examination|Bone marrow biopsy]], although not recommended may be helpful if there is suspicion of other disorders that can cause [[Lymphocytopenia|lymphopenia]], but there is not enough evidence to support [[bone marrow biopsy]] in COVID-19 patients.
*To view other diagnostic studies for COVID-19, [[COVID-19 other diagnostic studies|click here]].
 
==Treatment==
===Medical therapy===
'''Immune-Based Therapy''':
*There are insufficient data to recommend either for or against the use of [[COVID-19]] [[convalescent]] [[Plasma (blood)|plasma]] or [[SARS-CoV-2]] [[Immune globulin|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 [[Intravenous immunoglobulin|IVIG]] when it is otherwise indicated for the treatment of complications that arise during the course 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|Interleukin-1]] [[Inhibitor|inhibitors]] (e.g., [[anakinra]])
**[[Interleukin-6]] [[Inhibitor|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:
**[[Interferon|Interferons]], because of the lack of efficacy in the treatment of [[severe acute respiratory syndrome]] ([[SARS]]) and the [[Middle East respiratory syndrome]] ([[MERS]]) and [[toxicity]].
**[[Janus kinase]] inhibitors (e.g., [[baricitinib]]), because of their broad [[immunosuppressive]] effect.
 
===Surgery===
*Surgical intervention is not recommended for the management of [[COVID-19]] associated [[lymphopenia]].
===Primary Prevention===
*There are no established measures for the [[primary prevention]] of [[COVID-19]] associated [[lymphopenia]].
===Secondary Prevention===
*There are no established measures for the [[secondary prevention]] of [[COVID-19]] associated [[lymphopenia]].
==References==
{{reflist|2}}
{{reflist|2}}
 
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Latest revision as of 13:34, 24 July 2020

Main article: COVID-19

For COVID-19 frequently asked inpatient questions, click here
For COVID-19 frequently asked outpatient questions, click here

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Oluwabusola Fausat Adogba, MD[2]

Synonyms and keywords:Lymphocyte changes in COVID-19, sars-cov-2 related lymphopenia

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 in covid19 infection are direct infection of lymphocyte, direct destroying of lymphocytic organs, inflammatory cytokines such as TNFɑ, IL-6, lymphocyte inhibition.

Historical Perspective

Classification

  • There is no established system for the classification regarding COVID-19 related lymphopenia.

Pathophysiology

Causes

Differentiating COVID-19 related Lymphocytopenia from other Diseases

Epidemiology and Demographics

Risk Factors

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 complete blood count (CBC) with differential can be used for monitoring and predicting disease progression and severity in patients.

Natural History, Complications, and Prognosis

Diagnosis

Diagnostic Choice of Study

History and Symptoms

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.
  • For more information about COVID-19 physical examination please click here.

Laboratory findings

Electrocardiogram

X-ray

Echocardiography or Ultrasound

CT Scan

MRI

Other imaging findings

Other Diagnostic studies

Treatment

Medical therapy

Immune-Based Therapy:

  • 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.

Surgery

  • Surgical intervention is not recommended for the management of COVID-19 associated lymphopenia.

Primary Prevention

Secondary Prevention

References

  1. ↑ "WHO Western Pacific | World Health Organization".
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:77 ISBN 1591032016
  7. ↑ Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:68 ISBN 140510368X
  8. ↑ "WHO Coronavirus Disease (COVID-19) Dashboard | WHO Coronavirus Disease (COVID-19) Dashboard".
  9. ↑ "People Who Are at Higher Risk for Severe Illness | Coronavirus | COVID-19 | CDC".
  10. ↑ 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.
  11. ↑ "Management of Patients with Confirmed 2019-nCoV | CDC".
  12. ↑ 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.
  13. ↑ Fathi, Nazanin; Rezaei, Nima (2020). "Lymphopenia in COVID‐19: Therapeutic opportunities". Cell Biology International. doi:10.1002/cbin.11403. ISSN 1065-6995.
  14. ↑ "Symptoms of Coronavirus | CDC".

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