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}}
{{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]]. 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 to 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]] <br />


==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 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.
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 [[influenza]]
* [[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 [[Snakebites|snakebite]]
**After [[influenza]]
*[[Anesthesia]]
**After [[Snakebites|snakebite]]
* Antibody deficiency syndrome
**[[Anesthesia]]
*[[Aplastic Anemia]]
** Antibody deficiency syndrome
*[[Banti's Syndrome]]
**[[Aplastic Anemia]]
*[[Burns]]
**[[Banti's Syndrome]]
*Congenital immune deficiency
**[[Burns]]
*[[Cushing's Disease]]
**Congenital immune deficiency
*[[Dermatomyositis]]
**[[Cushing's Disease]]
*[[Drugs]], toxins
**[[Dermatomyositis]]
*[[Exudative enteropathy]]
**[[Drugs]], toxins
*[[Felty's Syndrome]]
**[[Exudative enteropathy]]
*Heavy [[exercise]]
**[[Felty's Syndrome]]
*[[HIV]]
**Heavy [[exercise]]
*[[Hodgkin's Lymphoma]]
**[[HIV]]
*[[Inflammatory Bowel Disease]]
**[[Hodgkin's Lymphoma]]
*Lymphocyte [[tuberculosis]]
**[[Inflammatory Bowel Disease]]
*[[Measles]]
**[[Lymphocyte]] [[tuberculosis]]
*[[Paroxysmal nocturnal hemoglobinuria]]
**[[Measles]]
*[[Polycythemia]]
**[[Paroxysmal nocturnal hemoglobinuria]]
*Postoperative
**[[Polycythemia]]
*[[Pregnancy]]
**Postoperative
*[[Sarcoidosis]]
**[[Pregnancy]]
*[[Scarlet Fever]]
**[[Sarcoidosis]]
*Secondary [[hypersplenism]]
**[[Scarlet Fever]]
*Single non-Hodgkin's [[lymphoma]]s
**Secondary [[hypersplenism]]
*[[Surgery]]
**Single [[Non-Hodgkin lymphoma|non-Hodgkin's lymphomas]]
*[[Systemic Lupus Erythematosus]]
**[[Surgery]]
*[[Trauma]]
**[[Systemic Lupus Erythematosus]]
*[[Tuberculosis]]
**[[Trauma]]
*[[Uremia]]
**[[Tuberculosis]]
*[[Whipple's Disease]]
**[[Uremia]]
*[[Zinc deficiency]]
**[[Whipple's Disease]]
 
**[[Zinc deficiency]]
<br />


==Epidemiology and Demographics==
==Epidemiology and Demographics==
The incidence/prevalence of [disease name] is approximately [number range] per 100,000 individuals worldwide.
*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]].
OR
 
In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.
 
OR
 
In [year], the incidence of [disease name] is approximately [number range] per 100,000 individuals with a case-fatality rate of [number range]%.
 
 
 
Patients of all age groups may develop [disease name].
 
OR
 
The incidence of [disease name] increases with age; the median age at diagnosis is [#] years.
 
OR
 
[Disease name] commonly affects individuals younger than/older than [number of years] years of age.
 
OR
 
[Chronic disease name] is usually first diagnosed among [age group].
 
OR
 
[Acute disease name] commonly affects [age group].
 
 
 
There is no racial predilection to [disease name].
 
OR
 
[Disease name] usually affects individuals of the [race 1] race. [Race 2] individuals are less likely to develop [disease name].
 
 
 
[Disease name] affects men and women equally.
 
OR
 
[Gender 1] are more commonly affected by [disease name] than [gender 2]. The [gender 1] to [gender 2] ratio is approximately [number > 1] to 1.
 
 
 
The majority of [disease name] cases are reported in [geographical region].
 
OR
 
[Disease name] is a common/rare disease that tends to affect [patient population 1] and [patient population 2].


==Risk Factors==
==Risk Factors==
There are no established risk factors for [disease name].
OR
The most potent risk factor in the development of [disease name] is [risk factor 1]. Other risk factors include [risk factor 2], [risk factor 3], and [risk factor 4].


OR
* 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]]
Common risk factors in the development of [disease name] include [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].
**[[Chronic obstructive pulmonary disease]]
 
**[[Immunocompromised]] state (weakened [[immune system]]) from solid [[organ transplant]]
OR
**<nowiki/>[[Obesity]] (body mass index [<nowiki/>[[Body mass index|BMI]]] of 30 or higher)
 
**Serious [[Heart condition|heart conditions]], <nowiki/>such as [[heart failure]], [[coronary artery disease]], or [[cardiomyopathies]]
Common risk factors in the development of [disease name] may be occupational, environmental, genetic, and viral.
**[[Sickle cell disease]]
**[[Type 2 diabetes mellitus]]


==Screening==
==Screening==
There is insufficient evidence to recommend routine screening for [disease/malignancy].
*[[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>
 
*A routine [[complete blood count]] ([[Complete blood count|CBC]]) with differential can be used for monitoring and predicting disease progression and severity in patients.
OR
 
According to the [guideline name], screening for [disease name] is not recommended.
 
OR
 
According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with [condition 1], [condition 2], and [condition 3].


==Natural History, Complications, and Prognosis==
==Natural History, Complications, and Prognosis==
If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
*[[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>
 
*[[COVID-19]] related [[lymphocytopenia]] starts acutely in the course of the disease, with other manifestations of the disease.
OR
*[[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>
Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
*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]].
OR
 
Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.


==Diagnosis==
==Diagnosis==
===Diagnostic Study of Choice===
===Diagnostic Choice of Study===
The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: [criterion 1], [criterion 2], [criterion 3], and [criterion 4].
 
OR
 
The diagnosis of [disease name] is based on the [criteria name] criteria, which include [criterion 1], [criterion 2], and [criterion 3].
 
OR
 
The diagnosis of [disease name] is based on the [definition name] definition, which includes [criterion 1], [criterion 2], and [criterion 3].
 
OR


There are no established criteria for the diagnosis of [disease name].
* [[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]]:
**[[Complete blood count]] ([[CBC]])
**[[Flow cytometry]]


===History and Symptoms===
===History and Symptoms===
The majority of patients with [disease name] are asymptomatic.
OR


The hallmark of [disease name] is [finding]. A positive history of [finding 1] and [finding 2] is suggestive of [disease name]. The most common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3]. Common symptoms of [disease] include [symptom 1], [symptom 2], and [symptom 3]. Less common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3].
* [[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>
**[[Fever]] or [[chills]]
**[[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===
===Physical Examination===
Patients with [disease name] usually appear [general appearance]. Physical examination of patients with [disease name] is usually remarkable for [finding 1], [finding 2], and [finding 3].
*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.
OR
*For more information about [[COVID-19]] physical examination please click [[COVID-19 physical examination|here]].
 
Common physical examination findings of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
The presence of [finding(s)] on physical examination is diagnostic of [disease name].
 
OR
 
The presence of [finding(s)] on physical examination is highly suggestive of [disease name].
 
===Laboratory Findings===
An elevated/reduced concentration of serum/blood/urinary/CSF/other [lab test] is diagnostic of [disease name].
 
OR
 
Laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].


OR
===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>
[Test] is usually normal among patients with [disease name].
*[[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]].
OR
 
Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication].
 
OR
 
There are no diagnostic laboratory findings associated with [disease name].


===Electrocardiogram===
===Electrocardiogram===
There are no ECG findings associated with [disease name].
* 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]].
OR
 
An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].


===X-ray===
===X-ray===
There are no x-ray findings associated with [disease name].
* 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]].
OR
 
An x-ray may be helpful in the diagnosis of [disease name]. Findings on an x-ray suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
There are no x-ray findings associated with [disease name]. However, an x-ray may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].


===Echocardiography or Ultrasound===
===Echocardiography or Ultrasound===
There are no echocardiography/ultrasound findings associated with [disease name].
* 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]].
OR
 
Echocardiography/ultrasound  may be helpful in the diagnosis of [disease name]. Findings on an echocardiography/ultrasound suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
There are no echocardiography/ultrasound  findings associated with [disease name]. However, an echocardiography/ultrasound  may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].


===CT scan===
===CT Scan===
There are no CT scan findings associated with [disease name].
* 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]].
OR
 
[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].


===MRI===
===MRI===
There are no MRI findings associated with [disease name].
* 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]].
OR
 
[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
 
===Other Imaging Findings===
There are no other imaging findings associated with [disease name].
 
OR
 
[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
===Other Diagnostic Studies===
There are no other diagnostic studies associated with [disease name].
 
OR
 
[Diagnostic study] may be helpful in the diagnosis of [disease name]. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].


OR
===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 for [disease name] include [diagnostic study 1], which demonstrates [finding 1], [finding 2], and [finding 3], and [diagnostic study 2], which demonstrates [finding 1], [finding 2], and [finding 3].
===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==
==Treatment==
===Medical Therapy===
===Medical therapy===
There is no treatment for [disease name]; the mainstay of therapy is supportive care.
'''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]].
OR
 
Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].
 
OR
 
The majority of cases of [disease name] are self-limited and require only supportive care.


OR
* 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]].


[Disease name] is a medical emergency and requires prompt treatment.
*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]])


OR
* 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]].
The mainstay of treatment for [disease name] is [therapy].
**[[Janus kinase]] inhibitors (e.g., [[baricitinib]]), because of their broad [[immunosuppressive]] effect.
 
OR
 
The optimal therapy for [malignancy name] depends on the stage at diagnosis.
 
OR
 
[Therapy] is recommended among all patients who develop [disease name].
 
OR
 
Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
 
OR
 
Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
 
OR
 
Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
 
OR
 
Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].


===Surgery===
===Surgery===
Surgical intervention is not recommended for the management of [disease name].
*Surgical intervention is not recommended for the management of [[COVID-19]] associated [[lymphopenia]].
 
OR
 
Surgery is not the first-line treatment option for patients with [disease name]. Surgery is usually reserved for patients with either [indication 1], [indication 2], and [indication 3]
 
OR
 
The mainstay of treatment for [disease name] is medical therapy. Surgery is usually reserved for patients with either [indication 1], [indication 2], and/or [indication 3].
 
OR
 
The feasibility of surgery depends on the stage of [malignancy] at diagnosis.
 
OR
 
Surgery is the mainstay of treatment for [disease or malignancy].
 
===Primary Prevention===
===Primary Prevention===
There are no established measures for the primary prevention of [disease name].
*There are no established measures for the [[primary prevention]] of [[COVID-19]] associated [[lymphopenia]].
 
OR
 
There are no available vaccines against [disease name].
 
OR
 
Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
 
OR
 
[Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3].
 
===Secondary Prevention===
===Secondary Prevention===
There are no established measures for the secondary prevention of [disease name].
*There are no established measures for the [[secondary prevention]] of [[COVID-19]] associated [[lymphopenia]].
 
OR
 
Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].
 
==References==
==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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