COVID-19-associated neutrophilia: Difference between revisions
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==Overview== | ==Overview== | ||
[[Coronavirus]] disease 2019 ([[COVID-19]]) | [[Coronavirus]] disease 2019 ([[COVID-19]]) first emerged in Wuhan,China in late 2019. 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]] associated [[neutrophilia]]. Research suggests [[COVID-19]] associated [[neutrophilia]] could be the cause of the severe symptoms of [[COVID-19]], including [[acute respiratory distress syndrome]] ([[ARDS]]) and can be linked to the [[Neutrophil]] Extracellular Traps (NETs). [[Acute respiratory distress syndrome]] ([[ARDS]]), [[pulmonary inflammation]], thick [[mucus]] secretions in the airways, extensive [[lung]] damage, and blood clots are suggested to be a result of the action of [[Neutrophil|neutrophils]]. When [[Neutrophil|neutrophils]] detect [[Pathogen|pathogens]], they can expel their [[DNA]] in a web laced with toxic [[enzymes]] (called a Neutrophil Extracellular Trap) to attack them. These NETs capture and digest the unwanted [[pathogen]]. However, in cases of [[Acute respiratory distress syndrome|ARDS]], ([[COVID-19]] manifestation) they cause damage to the lungs and other organs. People of any age with certain underlying medical conditions are at increased risk for severe illness from [[COVID-19]]. Recent studies have shown the association of a high [[neutrophil]]-to-[[lymphocyte]] ratio (NLR) to severe forms of [[COVID-19]] disease. | ||
==Historical Perspective== | ==Historical Perspective== | ||
*[[Coronavirus]] disease 2019 ([[COVID-19]]) first emerged in Wuhan, China in late 2019.<ref name="urlWHO Western Pacific | World Health Organization">{{cite web |url=https://www.who.int/westernpacific/emergencies/covid-19 |title=WHO Western Pacific | World Health Organization |format= |work= |accessdate=}}</ref> | |||
*[[Coronavirus]] disease 2019 ([[COVID-19]]) | |||
* On March 12, 2020, the [[World Health Organization]] declared the [[COVID-19]] outbreak a [[pandemic]]. | * On March 12, 2020, the [[World Health Organization]] declared the [[COVID-19]] outbreak a [[pandemic]]. | ||
==Classification== | ==Classification== | ||
* There is no established system for the classification regarding [[COVID-19]] associated [[neutrophilia]]. | * There is no established system for the classification regarding [[COVID-19]] associated [[neutrophilia]]. | ||
==Pathophysiology== | ==Pathophysiology== | ||
*Study suggests [[COVID-19]] associated [[neutrophilia]] could be the cause of the severe symptoms of [[COVID-19]], including [[acute respiratory distress syndrome]] | *Study suggests [[COVID-19]] associated [[neutrophilia]] could be the cause of the severe symptoms of [[COVID-19]], including [[acute respiratory distress syndrome|acute respiratory distress syndrome (]][[Acute respiratory distress syndrome|ARDS]]). It can be linked to the Neutrophil Extracellular Traps (NETs). | ||
*[[Acute respiratory distress syndrome]] ([[ARDS]]), [[pulmonary inflammation]], thick mucus secretions in the airways, extensive lung damage, and blood clots are suggested to be | *[[Acute respiratory distress syndrome]] ([[ARDS]]), [[pulmonary inflammation]], thick mucus secretions in the airways, extensive lung damage, and blood clots are suggested to be a result of the action of [[Neutrophil|neutrophils]]. When [[Neutrophil|neutrophils]] detect pathogens, they can expel their [[DNA]] in a web laced with toxic enzymes (Neutrophil Extracellular Trap) to attack them. | ||
*These NETs capture and digest the unwanted [[pathogen]] | *These NETs capture and digest the unwanted [[pathogen]], however, in cases of [[Acute respiratory distress syndrome|ARDS]] ([[COVID-19]] manifestation) they cause damage to the lungs and other organs. | ||
*[[Neutrophilia]] as an indicator for severe disease:<ref name="CicculloBorghetti2020">{{cite journal|last1=Ciccullo|first1=Arturo|last2=Borghetti|first2=Alberto|last3=Zileri Dal Verme|first3=Lorenzo|last4=Tosoni|first4=Alberto|last5=Lombardi|first5=Francesca|last6=Garcovich|first6=Matteo|last7=Biscetti|first7=Federico|last8=Montalto|first8=Massimo|last9=Cauda|first9=Roberto|last10=Di Giambenedetto|first10=Simona|title=Neutrophil-to-lymphocyte ratio and clinical outcome in COVID-19: a report from the Italian front line|journal=International Journal of Antimicrobial Agents|year=2020|pages=106017|issn=09248579|doi=10.1016/j.ijantimicag.2020.106017}}</ref> | *[[Neutrophilia]] as an indicator for severe disease:<ref name="CicculloBorghetti2020">{{cite journal|last1=Ciccullo|first1=Arturo|last2=Borghetti|first2=Alberto|last3=Zileri Dal Verme|first3=Lorenzo|last4=Tosoni|first4=Alberto|last5=Lombardi|first5=Francesca|last6=Garcovich|first6=Matteo|last7=Biscetti|first7=Federico|last8=Montalto|first8=Massimo|last9=Cauda|first9=Roberto|last10=Di Giambenedetto|first10=Simona|title=Neutrophil-to-lymphocyte ratio and clinical outcome in COVID-19: a report from the Italian front line|journal=International Journal of Antimicrobial Agents|year=2020|pages=106017|issn=09248579|doi=10.1016/j.ijantimicag.2020.106017}}</ref> | ||
**Recent studies have shown the association of a high [[neutrophil]]-to-[[lymphocyte]] ratio (NLR) to severe forms of [[COVID-19]] disease. | **Recent studies have shown the association of a high [[neutrophil]]-to-[[lymphocyte]] ratio (NLR) to severe forms of [[COVID-19]] disease. | ||
| Line 32: | Line 30: | ||
==Causes== | ==Causes== | ||
The SARS-CoV-2 [[COVID-19]] viral infection is the known cause of neutrophilia associated disease in infected patients. | * The [[SARS-CoV-2]] [[COVID-19]] viral infection is the known cause of [[neutrophilia]] associated disease in infected patients. | ||
==Differentiating COVID-19 related Neutrophilia from other Diseases== | ==Differentiating COVID-19 related Neutrophilia from other Diseases== | ||
*Acute infections | * [[COVID-19]] related [[neutrophilia]] starts acutely in the course of the disease, with other manifestations of the disease. [[Neutrophilia]] can occur in the following conditions:<ref name="WalkerWarnatz2006">{{cite journal|last1=Walker|first1=Ulrich A|last2=Warnatz|first2=Klaus|title=Idiopathic CD4 lymphocytopenia|journal=Current Opinion in Rheumatology|volume=18|issue=4|year=2006|pages=389–395|issn=1040-8711|doi=10.1097/01.bor.0000231908.57913.2f}}</ref> | ||
**Bacteria - Staphyloccoci, | **[[Acute (medicine)|Acute]] infections | ||
**Virus- Varicella, | ***[[Bacteria]] - Staphyloccoci, [[streptococci]], [[meningococci]] | ||
**Fungi- Candida, Coccidioides | ***[[Virus (biology)|Virus]]- [[Varicella]], [[herpes zoster]] | ||
*Non-infectious inflammation | ***[[Fungi]]- [[Candida]], [[Coccidioides spp|coccidioides]] | ||
**[[Rheumatic fever]] | **Non-infectious inflammation | ||
**[[Acute glomerulonephritis]] | ***[[Rheumatic fever]] | ||
**Collagen- | ***[[Acute glomerulonephritis]] | ||
**[[Diabetic ketoacidosis]] | ***[[Collagen-vascular diseases]] | ||
***[[Diabetic ketoacidosis]] | |||
==Epidemiology and Demographics== | ==Epidemiology and Demographics== | ||
*The incidence of the | *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 | WHO Coronavirus Disease (COVID-19) Dashboard |format= |work= |accessdate=}}</ref> | ||
*Patients of all age groups may develop COVID-19. However, the elderly | *Patients of all age groups may develop [[COVID-19]]. However, the elderly 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 | Coronavirus | COVID-19 | 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 | Coronavirus | COVID-19 | 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 ( | **[[Immunocompromised]] state (weakened [[immune system]]) from solid organ transplant | ||
*Serious heart conditions, such as [[heart failure]], [[coronary artery disease]], or [[cardiomyopathies]] | **[[Obesity]] ([[Body mass index]] ([[Body mass index|BMI]]) of 30 or higher) | ||
*[[Sickle cell disease]] | **Serious heart conditions, such as [[heart failure]], [[coronary artery disease]], or [[cardiomyopathies]] | ||
*[[Type 2 diabetes mellitus]] | **[[Sickle cell disease]] | ||
**[[Type 2 diabetes mellitus]] | |||
==Screening== | ==Screening== | ||
*A high | *A high [[neutrophil]]-to-[[lymphocyte]] ratio has been linked to [[Intensive care unit|ICU]] admission. A routine [[complete blood count]] ([[Complete blood count|CBC]]) test should be done in [[COVID-19]] patients for early detection. | ||
==Natural History, Complications, and Prognosis== | ==Natural History, Complications, and Prognosis== | ||
*Common hematologic complications of [[coronavirus]] include [[COVID-19-associated lymphopenia|lymphopenia]], [[ | *Common [[hematologic]] complications of [[coronavirus]] include [[COVID-19-associated lymphopenia|lymphopenia]], [[neutrophilia]] and [[COVID-19-associated thrombocytopenia|thrombocytosis]]. | ||
* | *The [[pathogenesis]] of the [[cytokine storm]] associated with [[neutrophilia]] in [[COVID-19]] patients is unclear. | ||
*It has, however, been associated with poor outcomes in patients. The neutrophil-to-[[lymphocyte]] ratio has been identified as an independent risk factor for severe disease in [[COVID-19]] patients.<ref name="EgebladZuo2020">{{cite journal|last1=Egeblad|first1=Mikala|last2=Zuo|first2=Yu|last3=Weber|first3=Andrew|last4=Yost|first4=Christian C.|last5=Spicer|first5=Jonathan D.|last6=Schwartz|first6=Robert E.|last7=Salvatore|first7=Steven|last8=Rousseau|first8=Simon|last9=Renaud|first9=Stephane|last10=Rayes|first10=Roni|last11=McAllister|first11=Florencia|last12=Looney|first12=Mark R.|last13=Loda|first13=Massimo|last14=Knight|first14=Jason S.|last15=Huynh|first15=Caroline|last16=Guerci|first16=Philippe|last17=Daßler-Plenker|first17=Juliane|last18=Crawford|first18=James M.|last19=Cools-Lartigue|first19=Jonathan|last20=Borczuk|first20=Alain|last21=Baxter-Stoltzfus|first21=Amelia|last22=Adrover|first22=Jose M.|last23=Barnes|first23=Betsy J.|title=Targeting potential drivers of COVID-19: Neutrophil extracellular traps|journal=Journal of Experimental Medicine|volume=217|issue=6|year=2020|issn=0022-1007|doi=10.1084/jem.20200652}}</ref> | |||
==Diagnosis== | ==Diagnosis== | ||
===Diagnostic study of Choice === | ===Diagnostic study of Choice === | ||
*Peripheral white blood cell count on a CBC with differential test | *Peripheral [[white blood cell count]] on a [[Complete blood count|CBC]] with differential test | ||
*Neutrophil-lymphocyte ratio | *[[Neutrophil]]-[[lymphocyte]] ratio | ||
*C-reactive protein | *[[C-reactive protein]] | ||
*Erythrocyte sedimentation rate | *[[Erythrocyte sedimentation rate]] | ||
===History and Symptoms=== | ===History and Symptoms=== | ||
*[[Fever]] or [[chills]] | * [[Neutrophilia]] 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 | CDC |format= |work= |accessdate=}}</ref> | ||
*[[Cough]] | **[[Fever]] or [[chills]] | ||
*Shortness of breath or difficulty breathing | **[[Cough]] | ||
*[[Fatigue]] | **[[Shortness of breath]] (SOB) or [[difficulty breathing]] | ||
*[[Muscle]] or [[body aches]] | **[[Fatigue]] | ||
*[[Headache]] | **[[Muscle]] or [[body aches]] | ||
*New loss of taste or smell | **[[Headache]] | ||
*Sore throat | **New loss of taste or [[smell]] | ||
*[[Congestion]] or [[runny nose]] | **Sore throat | ||
*[[Nausea]] or [[vomiting]] | **[[Congestion]] or [[runny nose]] | ||
*[[Diarrhea]] | **[[Nausea]] or [[vomiting]] | ||
**[[Diarrhea]] | |||
===Physical Examination=== | ===Physical Examination=== | ||
There are no physical findings associated with COVID-19 associated neutrophilia. | * There are no physical findings associated with [[COVID-19]] associated [[neutrophilia]]. | ||
For COVID-19 Physical examination click [[COVID-19 physical examination|here]]. | * For COVID-19 Physical examination click [[COVID-19 physical examination|here]]. | ||
===Laboratory findings=== | ===Laboratory findings=== | ||
* Increased [[Neutrophil|neutrophils]] on [[Complete blood count|CBC]] | |||
* Increased neutrophils on CBC | * Increased [[inflammatory]] markers such as [[Interleukin 6|IL-6,]] [[C-reactive protein|CRP]] | ||
* Increased inflammatory markers such as [[Interleukin 6|IL-6,]] [[C-reactive protein|CRP]] | * For more information about [[COVID-19]] related laboratory findings please click [[COVID-19 laboratory findings|here]]. | ||
* For more | |||
===Electrocardiogram=== | ===Electrocardiogram=== | ||
* There are no [[The electrocardiogram|ECG]] findings associated with [[COVID-19]] associated [[neutrophilia]]. | |||
* There are no ECG findings associated with [[COVID-19]] associated neutrophilia. | * To view the [[electrocardiogram]] findings on [[COVID-19]], [[COVID-19 electrocardiogram|click here]]. | ||
* To view the electrocardiogram findings on COVID-19, [[COVID-19 electrocardiogram|click here]]. | |||
===X-ray=== | ===X-ray=== | ||
* There are no [[X-rays|X-ray]] findings associated with [[COVID-19]] associated [[neutrophilia]]. | |||
* There are no X-ray findings associated with [[COVID-19]] associated neutrophilia. | * To view [[X-rays|X-ray]] findings of COVID-19 ,click [[COVID-19 x ray|here]]. | ||
* To view X-ray findings of COVID-19 ,click [[COVID-19 x ray|here]]. | |||
===Echocardiography or Ultrasound=== | ===Echocardiography or Ultrasound=== | ||
* There are no [[echocardiography]] or [[ultrasound]] findings associated with [[COVID-19]] associated [[neutrophilia]]. | |||
* There are no echocardiography or ultrasound findings associated with [[COVID-19]] associated neutrophilia. | * To view the [[Echocardiography|echocardiographic]] findings on [[COVID-19]], [[COVID-19 echocardiography and ultrasound|click here]]. | ||
* To view the echocardiographic findings on COVID-19, [[COVID-19 echocardiography and ultrasound|click here]]. | |||
===CT Scan=== | ===CT Scan=== | ||
* There are no [[Computed tomography|CT]] scan findings associated with [[COVID-19]] associated [[neutrophilia]]. | |||
* There are no CT scan findings associated with [[COVID-19]] associated neutrophilia. | * To view the [[Computed tomography|CT]] scan findings on [[COVID-19]], [[COVID-19 CT scan|click here]]. | ||
* To view the CT scan findings on COVID-19, [[COVID-19 CT scan|click here]]. | |||
===MRI=== | ===MRI=== | ||
* There are no [[Magnetic resonance imaging|MRI]] findings associated with [[COVID-19]] associated [[neutrophilia]]. | |||
* There are no MRI findings associated with [[COVID-19]] associated neutrophilia. | * To view the [[Magnetic resonance imaging|MRI]] findings on [[COVID-19]], [[COVID-19 MRI|click here]]. | ||
* To view the MRI findings on COVID-19, [[COVID-19 MRI|click here]]. | |||
===Other imaging findings=== | ===Other imaging findings=== | ||
* There are no other imaging findings associated with [[COVID-19]] associated [[neutrophilia]]. | |||
* | * To view other imaging findings on [[COVID-19]], [[COVID-19 other imaging findings|click here]]. | ||
===Other Diagnostic studies=== | ===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 neutrophilia , 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 suspicion of other disorders that can cause [[neutrophilia]] , 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]]. | *To view other diagnostic studies for [[COVID-19]], [[COVID-19 other diagnostic studies|click here]]. | ||
==Treatment== | ==Treatment== | ||
===Medical therapy=== | ===Medical therapy=== | ||
Immune-Based Therapy: | Immune-Based Therapy: | ||
*There | *There is insufficient data to recommend either for or against the use of [[COVID-19]] [[convalescent]] [[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 ([[Intravenous immunoglobulin|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]]. | * The [[COVID-19]] Treatment Guidelines Panel (the Panel) recommends against the use of non-[[SARS-CoV-2]]-specific [[intravenous]] [[immune globulin]] ([[Intravenous immunoglobulin|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]]:<ref name="ZhongTang2020">{{cite journal|last1=Zhong|first1=Jixin|last2=Tang|first2=Jungen|last3=Ye|first3=Cong|last4=Dong|first4=Lingli|title=The immunology of COVID-19: is immune modulation an option for treatment?|journal=The Lancet Rheumatology|volume=2|issue=7|year=2020|pages=e428–e436|issn=26659913|doi=10.1016/S2665-9913(20)30120-X}}</ref> | |||
**[[Interleukin 1|Interleukin-1]] inhibitors (e.g., [[Anakinra]]) | |||
**[[Interleukin-6]] inhibitors (e.g., [[Sarilumab]], [[siltuximab]], [[tocilizumab]]) | |||
* [[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 [[Immunomodulator|immunomodulators]], such as : | ||
* Janus kinase inhibitors (e.g., [[baricitinib]]), because of their broad [[immunosuppressive]] effect. | |||
* [[Interferons]], because of the lack of efficacy in the treatment of [[severe acute respiratory syndrome]] ([[Severe acute respiratory syndrome|SARS]]) and [[Middle East respiratory syndrome]] ([[Middle East respiratory syndrome coronavirus infection|MERS]]) and toxicity. | |||
*[[Janus kinase]] inhibitors (e.g., [[baricitinib]]), because of their broad [[immunosuppressive]] effect. | |||
===Surgery=== | ===Surgery=== | ||
Surgical intervention is not recommended for the management of COVID-19 associated neutrophilia. | * Surgical intervention is not recommended for the management of [[COVID-19]] associated [[neutrophilia]]. | ||
===Primary Prevention=== | ===Primary Prevention=== | ||
There are no established measures for the primary prevention of COVID-19 associated neutrophilia. | * There are no established measures for the [[primary prevention]] of [[COVID-19]] associated [[neutrophilia]]. | ||
===Secondary Prevention=== | ===Secondary Prevention=== | ||
There are no established measures for the secondary prevention | * There are no established measures for the secondary prevention of [[COVID-19]] associated [[neutrophilia]]. | ||
==References== | ==References== | ||
{{reflist|2}} | {{reflist|2}} | ||
[[Category: Up-To-Date]] | |||
{{WikiDoc Help Menu}} | {{WikiDoc Help Menu}} | ||
{{WikiDoc Sources}} | {{WikiDoc Sources}} | ||
Latest revision as of 15:25, 4 August 2020
For COVID-19 frequently asked inpatient questions, click here
For COVID-19 frequently asked outpatient questions, click here
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Oluwabusola Fausat Adogba, MD[2]
Synonyms and keywords:WBC changes in COVID-19, SARS-COV2 related neutrophilia
Overview
Coronavirus disease 2019 (COVID-19) first emerged in Wuhan,China in late 2019. 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 associated neutrophilia. Research suggests COVID-19 associated neutrophilia could be the cause of the severe symptoms of COVID-19, including acute respiratory distress syndrome (ARDS) and can be linked to the Neutrophil Extracellular Traps (NETs). Acute respiratory distress syndrome (ARDS), pulmonary inflammation, thick mucus secretions in the airways, extensive lung damage, and blood clots are suggested to be a result of the action of neutrophils. When neutrophils detect pathogens, they can expel their DNA in a web laced with toxic enzymes (called a Neutrophil Extracellular Trap) to attack them. These NETs capture and digest the unwanted pathogen. However, in cases of ARDS, (COVID-19 manifestation) they cause damage to the lungs and other organs. People of any age with certain underlying medical conditions are at increased risk for severe illness from COVID-19. Recent studies have shown the association of a high neutrophil-to-lymphocyte ratio (NLR) to severe forms of COVID-19 disease.
Historical Perspective
- Coronavirus disease 2019 (COVID-19) first emerged in Wuhan, China in late 2019.[1]
- On March 12, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic.
Classification
- There is no established system for the classification regarding COVID-19 associated neutrophilia.
Pathophysiology
- Study suggests COVID-19 associated neutrophilia could be the cause of the severe symptoms of COVID-19, including acute respiratory distress syndrome (ARDS). It can be linked to the Neutrophil Extracellular Traps (NETs).
- Acute respiratory distress syndrome (ARDS), pulmonary inflammation, thick mucus secretions in the airways, extensive lung damage, and blood clots are suggested to be a result of the action of neutrophils. When neutrophils detect pathogens, they can expel their DNA in a web laced with toxic enzymes (Neutrophil Extracellular Trap) to attack them.
- These NETs capture and digest the unwanted pathogen, however, in cases of ARDS (COVID-19 manifestation) they cause damage to the lungs and other organs.
- Neutrophilia as an indicator for severe disease:[2]
- Recent studies have shown the association of a high neutrophil-to-lymphocyte ratio (NLR) to severe forms of COVID-19 disease.
- NLR >4 on admission has been linked to ICU admission.
- COVID-19 patients with severe disease presentation had a higher NLR on admission compared to patients with a milder COVID-19 disease presentation.
Causes
- The SARS-CoV-2 COVID-19 viral infection is the known cause of neutrophilia associated disease in infected patients.
- COVID-19 related neutrophilia starts acutely in the course of the disease, with other manifestations of the disease. Neutrophilia can occur in the following conditions:[3]
- Acute infections
- Bacteria - Staphyloccoci, streptococci, meningococci
- Virus- Varicella, herpes zoster
- Fungi- Candida, coccidioides
- Non-infectious inflammation
- Acute infections
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.[4]
- Patients of all age groups may develop COVID-19. However, the elderly 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:[5]
- 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
- A high neutrophil-to-lymphocyte ratio has been linked to ICU admission. A routine complete blood count (CBC) test should be done in COVID-19 patients for early detection.
Natural History, Complications, and Prognosis
- Common hematologic complications of coronavirus include lymphopenia, neutrophilia and thrombocytosis.
- The pathogenesis of the cytokine storm associated with neutrophilia in COVID-19 patients is unclear.
- It has, however, been associated with poor outcomes in patients. The neutrophil-to-lymphocyte ratio has been identified as an independent risk factor for severe disease in COVID-19 patients.[6]
Diagnosis
Diagnostic study of Choice
- Peripheral white blood cell count on a CBC with differential test
- Neutrophil-lymphocyte ratio
- C-reactive protein
- Erythrocyte sedimentation rate
History and Symptoms
- Neutrophilia 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:[7]
- Fever or chills
- Cough
- Shortness of breath (SOB) 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 COVID-19 associated neutrophilia.
- For COVID-19 Physical examination click here.
Laboratory findings
- Increased neutrophils on CBC
- Increased inflammatory markers such as IL-6, CRP
- For more information about COVID-19 related laboratory findings please click here.
Electrocardiogram
- There are no ECG findings associated with COVID-19 associated neutrophilia.
- To view the electrocardiogram findings on COVID-19, click here.
X-ray
- There are no X-ray findings associated with COVID-19 associated neutrophilia.
- To view X-ray findings of COVID-19 ,click here.
Echocardiography or Ultrasound
- There are no echocardiography or ultrasound findings associated with COVID-19 associated neutrophilia.
- To view the echocardiographic findings on COVID-19, click here.
CT Scan
- There are no CT scan findings associated with COVID-19 associated neutrophilia.
- To view the CT scan findings on COVID-19, click here.
MRI
- There are no MRI findings associated with COVID-19 associated neutrophilia.
- To view the MRI findings on COVID-19, click here.
Other imaging findings
- There are no other imaging findings associated with COVID-19 associated neutrophilia.
- To view other imaging findings on COVID-19, click here.
Other Diagnostic studies
- Bone marrow biopsy, although not recommended may be helpful if there is suspicion of other disorders that can cause neutrophilia , but there is not enough evidence to support bone marrow biopsy in COVID-19 patients.
- To view other diagnostic studies for COVID-19, click here.
Treatment
Medical therapy
Immune-Based Therapy:
- There is 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.
- There are insufficient data to recommend either for or against the use of the following agents for the treatment of COVID-19:[8]
- 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 the 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.
Surgery
- Surgical intervention is not recommended for the management of COVID-19 associated neutrophilia.
Primary Prevention
- There are no established measures for the primary prevention of COVID-19 associated neutrophilia.
Secondary Prevention
- There are no established measures for the secondary prevention of COVID-19 associated neutrophilia.
References
- ↑ "WHO Western Pacific | World Health Organization".
- ↑ Ciccullo, Arturo; Borghetti, Alberto; Zileri Dal Verme, Lorenzo; Tosoni, Alberto; Lombardi, Francesca; Garcovich, Matteo; Biscetti, Federico; Montalto, Massimo; Cauda, Roberto; Di Giambenedetto, Simona (2020). "Neutrophil-to-lymphocyte ratio and clinical outcome in COVID-19: a report from the Italian front line". International Journal of Antimicrobial Agents: 106017. doi:10.1016/j.ijantimicag.2020.106017. ISSN 0924-8579.
- ↑ Walker, Ulrich A; Warnatz, Klaus (2006). "Idiopathic CD4 lymphocytopenia". Current Opinion in Rheumatology. 18 (4): 389–395. doi:10.1097/01.bor.0000231908.57913.2f. ISSN 1040-8711.
- ↑ Egeblad, Mikala; Zuo, Yu; Weber, Andrew; Yost, Christian C.; Spicer, Jonathan D.; Schwartz, Robert E.; Salvatore, Steven; Rousseau, Simon; Renaud, Stephane; Rayes, Roni; McAllister, Florencia; Looney, Mark R.; Loda, Massimo; Knight, Jason S.; Huynh, Caroline; Guerci, Philippe; Daßler-Plenker, Juliane; Crawford, James M.; Cools-Lartigue, Jonathan; Borczuk, Alain; Baxter-Stoltzfus, Amelia; Adrover, Jose M.; Barnes, Betsy J. (2020). "Targeting potential drivers of COVID-19: Neutrophil extracellular traps". Journal of Experimental Medicine. 217 (6). doi:10.1084/jem.20200652. ISSN 0022-1007.
- ↑ Zhong, Jixin; Tang, Jungen; Ye, Cong; Dong, Lingli (2020). "The immunology of COVID-19: is immune modulation an option for treatment?". The Lancet Rheumatology. 2 (7): e428–e436. doi:10.1016/S2665-9913(20)30120-X. ISSN 2665-9913.