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__NOTOC__  
__NOTOC__  
{{AE}} {{SHA}}
{{AE}} {{SHA}}
<br />
{| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
|+
|-
| colspan="9" style="background: #4479BA; text-align: center;" |{{fontcolor|#000|Some Differential Diagnosis of Asperger Syndrome
(Modified Table from The Investigation and Differential Diagnosis of Asperger Syndrome in Adults)<ref name="pmid24290364" /> '''}}
|- style="padding: 5px 5px; background: #4479BA;" align="center" |
| style="padding: 5px 5px; background: #4479BA;" align="center" |
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Asperger Syndrome'''
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Schizoid Personality Disorder'''
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Schizotypal Personality Disorder'''
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Avoidant Personality Disorder'''
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Social Phobia'''
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Obsessive Personality Disorder'''
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Obsessive-compulsive disorder (OCD)'''
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Attention deficit–hyperactivity disorder (ADHD)'''
|-
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Abnormal social interaction'''
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
|-
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Abnormal verbal communication'''
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
|-
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Abnormal facial expression/gestures/prosody'''
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
|-
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Abnormal eye contact'''
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
|-
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Abnormal theory of mind'''
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
|-
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Abnormal empathy'''
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
|-
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Abnormal interests/rituals/compulsions'''
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
|-
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Abnormal attention'''
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
|-
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Abnormal  psychomotor function'''
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
|-
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Abnormal self-injurious behavior'''
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +/-
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +/- <br />
|-
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Abnormal psychotic manifestations'''
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/-
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
|-
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Abnormal social interaction in childhood'''
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
|-
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Abnormal biographical stress factors'''
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +/- 
|}
== Cytokine Storm ==




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*** May be pro- or anti-[[Inflammation|inflammatory]]  
*** May be pro- or anti-[[Inflammation|inflammatory]]  
**'''Chemokines'''
**'''Chemokines'''
*** Act as chemotaxins
*** Act as chemoattractants
*** Recruitment of [[White blood cells|leukocytes]]
*** Recruitment of [[White blood cells|leukocytes]]
**'''Colony-stimulating factors'''  
**'''Colony-stimulating factors'''  
Line 60: Line 218:
**Decrease in [[Cytotoxic T cell|CD+8 T-cells]]
**Decrease in [[Cytotoxic T cell|CD+8 T-cells]]


*High levels of expression of IL-1B, IFN-γ , IP-10, and [[CCL2|monocyte hemoattractant protein 1 (MCP-1)]] have been detected in patients with [[COVID-19]].  
*It has been reported that in patients with [[COVID-19]] there is increase in IL-1B, IFN-γ , IP-10, and [[CCL2|monocyte hemoattractant protein 1 (MCP-1)]] and [[COVID-19]]  patients in the [[Intensive care unit|intensive care unit (ICU)]] have increased levels of [[granulocyte  colony-stimulating factor]], IP-10, [[CCL2|MCP-1]], macrophage inflammatory  protein-1A, and [[Tumor necrosis factor-alpha|TNF-α]] compared to those in general wards. However, in contrast to [[Severe acute respiratory syndrome|SARS infection]], patients with [[COVID-19]] infection have high levels of  [[Interleukin 4|IL-4]] and [[Interleukin 10|IL-10]] (secreted by [[Th2|Th2 cells]]), which are antiinflammatory [[Cytokine|cytokines]].<ref name="pmid31986264">{{cite journal| author=Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y | display-authors=etal| title=Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. | journal=Lancet | year= 2020 | volume= 395 | issue= 10223 | pages= 497-506 | pmid=31986264 | doi=10.1016/S0140-6736(20)30183-5 | pmc=7159299 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31986264  }} </ref>
*These inflammatory [[Cytokine|cytokines]] may activate the [[T helper cell|Thelper type 1 (Th1)]] cell response.47 [[T helper cell|Th1]] activation is a key event  in the activation of specific immunity.48
*The serum levels of IL-2R and [[Interleukin 6|IL-6]] in patients with [[COVID-19]] are positively correlated with the severity of the disease (i.e., critically ill patients > severely ill patients  > ordinary patients).49  
*ther studies have found that, compared  with [[COVID-19]] patients from general wards, patients in the [[Intensive care unit|intensive care unit (ICU)]] display increased serum levels of [[granulocyte  colony-stimulating factor]], IP-10, [[CCL2|MCP-1]], macrophage inflammatory  protein-1A, and [[Tumor necrosis factor-alpha|TNF-α]]. The above studies suggest that the cytokine storm is positively correlated with disease severity.47


*In contrast to [[Severe acute respiratory syndrome|SARS infection]], patients with [[COVID-19]] infection have high levels of  [[Interleukin 4|IL-4]] and [[Interleukin 10|IL-10]] (secreted  by [[Th2|Th2 cells]]), which are antiinflammatory [[Cytokine|cytokines]].


{| class="wikitable"
{| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
|+
|+
! colspan="3" |Cytokines Involved in COVID-19-Associated-Cytokine Storm
!colspan="9" style="background: #4479BA; text-align: center;" |{{fontcolor|#000|'''Cytokines Involved in COVID-19-Associated-Cytokine Storm'''}}
|-
|-
| rowspan="5" |'''Proinflammatory'''
| rowspan="5" style="padding: 5px 5px; background: #4479BA;" align="center" |{{fontcolor|#000|'''Proinflammatory'''}}
|'''Interferones'''
|style="padding: 5px 5px; background: #4479BA;" align="center" |'''Interferones'''
|
|style="padding: 5px 5px; background: #DCDCDC;" align="left" |
* IFN-γ
* IFN-γ
|-
|-
|'''Interleukines'''
|style="padding: 5px 5px; background: #4479BA;" align="center" |'''Interleukines'''
|
|style="padding: 5px 5px; background: #DCDCDC;" align="left" |
* IL-1β
*IL-1β
* IL-6
* IL-6
|-
|-
|'''Chemokines'''
|style="padding: 5px 5px; background: #4479BA;" align="center" |'''Chemokines'''
|
|style="padding: 5px 5px; background: #DCDCDC;" align="left" |
* CCL-2 (MCP-1)
*CCL-2 (MCP-1)
* CCL-3 (Macrophage inflammatory protein-1A)
* CCL-3 (Macrophage inflammatory protein-1A)
* CCL-5
* CCL-5
* IL-8 (CXCL8)  
* IL-8 (CXCL8)
* IP-10 (CXCL10)
* IP-10 (CXCL10)
|-
|-
|'''Colony-stimulating'''
|style="padding: 5px 5px; background: #4479BA;" align="center" |'''Colony-stimulating'''
'''factors  '''
'''factors  '''
|
|style="padding: 5px 5px; background: #DCDCDC;" align="left" |
* GM-CSF
* GM-CSF
|-
|-
|'''Tumor necrosis'''
|style="padding: 5px 5px; background: #4479BA;" align="center" |'''Tumor necrosis'''
'''factor  '''
'''factor  '''
|
|style="padding: 5px 5px; background: #DCDCDC;" align="left" |
* TNF-α
* TNF-α
|-
|-
|'''Anti-inflammatory'''
|style="padding: 5px 5px; background: #4479BA;" align="center" |{{fontcolor|#000|'''Anti-inflammatory'''}}
|'''Interleukines'''
|style="padding: 5px 5px; background: #4479BA;" align="center" |'''Interleukines'''
|
|style="padding: 5px 5px; background: #DCDCDC;" align="left" |
* IL-4
*IL-4
* IL-10
* IL-10
|}
|}


==Overview==


==COVID-19-Associated Hematologic Findings==


*[[Leukocytosis]]
*Increase in [[C-reactive protein|C-reactive protein (CRP)]]
*Increase in [[procalcitonin]]
*Increase in [[ferritin]]
*Increase in [[Aspartate aminotransferase|aspartate aminotransferase (AST)]]
*Increase in [[Alanine aminotransferase|alanine aminotransferase (ALT)]]
*Increase in [[Lactate dehydrogenase|lactate dehydrogenase (LDH)]]
*Increase in monocyte volume distribution width (MDW)
*Increase in total [[bilirubin]]
*Increase in creatinine
*Increase in cardiac [[Troponin|troponins]]
*Decrease in [[albumin]]
*Increase in [[Interleukin-6|interleukin-6 (IL-6)]]
*[[Thrombocytosis]]


<br />
==Pathophysiology and Causes==
 
==<s>Overview</s>==
 
==<s>COVID-19-Associated Hematologic Findings</s>==
 
*<s>[[Leukocytosis]]</s>
*<s>Increase in [[C-reactive protein|C-reactive protein (CRP)]]</s>
*<s>Increase in [[procalcitonin]]</s>
*<s>Increase in [[ferritin]]</s>
*<s>Increase in [[Aspartate aminotransferase|aspartate aminotransferase (AST)]]</s>
*<s>Increase in [[Alanine aminotransferase|alanine aminotransferase (ALT)]]</s>
*<s>Increase in [[Lactate dehydrogenase|lactate dehydrogenase (LDH)]]</s>
*<s>Increase in monocyte volume distribution width (MDW)</s>
*<s>Increase in total [[bilirubin]]</s>
*<s>Increase in creatinine</s>
*<s>Increase in cardiac [[Troponin|troponins]]</s>
*<s>Decrease in [[albumin]]</s>
*<s>Increase in [[Interleukin-6|interleukin-6 (IL-6)]]</s>
*<s>[[Thrombocytosis]]</s>


==<s>Pathophysiology and Causes</s>==
*CRP is an [[Acute phase protein|acute phase reactant]] that increases in conditions with inflammation.<ref name="pmid32311826">{{cite journal| author=Frater JL, Zini G, d'Onofrio G, Rogers HJ| title=COVID-19 and the clinical hematology laboratory. | journal=Int J Lab Hematol | year= 2020 | volume= 42 Suppl 1 | issue=  | pages= 11-18 | pmid=32311826 | doi=10.1111/ijlh.13229 | pmc=7264622 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32311826  }} </ref>
*In [[sepsis]], the activation and adherence of [[Monocyte|monocytes]] increase [[procalcitonin]], therefore [[procalcitonin]] in a biomarker for sepsis and septic shock.<ref name="pmid24982830">{{cite journal| author=Meisner M| title=Update on procalcitonin measurements. | journal=Ann Lab Med | year= 2014 | volume= 34 | issue= 4 | pages= 263-73 | pmid=24982830 | doi=10.3343/alm.2014.34.4.263 | pmc=4071182 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24982830  }} </ref>
*[[Alanine transaminase|ALT]] is produced by liver cells and is increased in liver conditions.<ref name="pmid32311826" />
*[[Lactate dehydrogenase|LDH]] is expressed in almost all cells and an increase in [[LDH]] could be seen in damage to any of the cell types.<ref name="pmid32311826" />
*[[Bilirubin]]  is produced by liver cells and increases in liver and biliary conditions.<ref name="pmid32311826" />
*Creatinin is produced in the liver and excreted by the kidneys; [[creatinine]] increases when there is decrease in [[glomerular filtration rate]].<ref name="pmid32311826" />
*Increase in cardiac [[Troponin|troponins]] are used for diagnosing myocardial infarction and [[Acute coronary syndromes|acute coronary syndrome]] .<ref name="pmid32311826" />
*[[Albumin]] may be decreased in many conditions such as [[sepsis]], renal disease or [[malnutrition]].<ref name="pmid32311826" />


*<s>CRP is an [[Acute phase protein|acute phase reactant]] that increases in conditions with inflammation.<ref name="pmid32311826">{{cite journal| author=Frater JL, Zini G, d'Onofrio G, Rogers HJ| title=COVID-19 and the clinical hematology laboratory. | journal=Int J Lab Hematol | year= 2020 | volume= 42 Suppl 1 | issue=  | pages= 11-18 | pmid=32311826 | doi=10.1111/ijlh.13229 | pmc=7264622 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32311826  }} </ref></s>
==Epidemiology==
*<s>In [[sepsis]], the activation and adherence of [[Monocyte|monocytes]] increase [[procalcitonin]], therefore [[procalcitonin]] in a biomarker for sepsis and septic shock.<ref name="pmid24982830">{{cite journal| author=Meisner M| title=Update on procalcitonin measurements. | journal=Ann Lab Med | year= 2014 | volume= 34 | issue= 4 | pages= 263-73 | pmid=24982830 | doi=10.3343/alm.2014.34.4.263 | pmc=4071182 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24982830  }} </ref></s>
*<s>[[Alanine transaminase|ALT]] is produced by liver cells and is increased in liver conditions.<ref name="pmid32311826" /></s>
*<s>[[Lactate dehydrogenase|LDH]] is expressed in almost all cells and an increase in [[LDH]] could be seen in damage to any of the cell types.<ref name="pmid32311826" /></s>
*<s>[[Bilirubin]]  is produced by liver cells and increases in liver and biliary conditions.<ref name="pmid32311826" /></s>
*<s>Creatinin is produced in the liver and excreted by the kidneys; [[creatinine]] increases when there is decrease in [[glomerular filtration rate]].<ref name="pmid32311826" /></s>
*<s>Increase in cardiac [[Troponin|troponins]] are used for diagnosing myocardial infarction and [[Acute coronary syndromes|acute coronary syndrome]] .<ref name="pmid32311826" /></s>
*<s>[[Albumin]] may be decreased in many conditions such as [[sepsis]], renal disease or [[malnutrition]].<ref name="pmid32311826" /></s>


==<s>Epidemiology</s>==
*[[Leukocytosis]] is seen in 11.4% of patients with severe [[COVID-19]] infection compared to 4.8% of patients with non-severe infection.<ref name="pmid32109013" /><ref name="pmid32191623">{{cite journal| author=Lippi G, Plebani M| title=The critical role of laboratory medicine during coronavirus disease 2019 (COVID-19) and other viral outbreaks. | journal=Clin Chem Lab Med | year= 2020 | volume= 58 | issue= 7 | pages= 1063-1069 | pmid=32191623 | doi=10.1515/cclm-2020-0240 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32191623  }} </ref>
*Increase in CRP is seen in 81.5% of patients with severe [[COVID-19]] infection compared to 56.4% of patients with non-severe infection.<ref name="pmid32109013" /><ref name="pmid32191623" />
*Increase in [[procalcitonin]] is seen in 13.7% of patients with severe [[COVID-19]] infection compared to 3.7% of patients with non-severe infection.<ref name="pmid32109013" /><ref name="pmid32191623" />
*Increase in [[Aspartate transaminase|AST]] is seen in 39.4% of patients with severe [[COVID-19]] infection compared to 18.2% of patients with non-severe infection.<ref name="pmid32109013" /><ref name="pmid32191623" />
*Increase in [[ALT]] is seen in 28.1% of patients with severe [[COVID-19]] infection compared to 19.8%  of patients with non-severe infection.<ref name="pmid32109013" /><ref name="pmid32191623" />
*Increase in [[Lactate dehydrogenase|LDH]] is seen in 58.1% of patients with severe [[COVID-19]] infection compared to 37.2% of patients with non-severe infection.<ref name="pmid32109013" /><ref name="pmid32191623" />
*MDW was found to be increased in all patients with COVID-19 infection, particularly in those with the worst conditions.<ref name="pmid32191623" />
*Increase in total bilirubin is seen in 13.3% of patients with severe [[COVID-19]] infection compared to 9.9% of patients with non-severe infection.<ref name="pmid32109013" /><ref name="pmid32191623" />
*Increase in [[creatinine]] is seen in 4.3% of patients with severe [[COVID-19]] infection compared to 1% of patients with non-severe infection.<ref name="pmid32109013" /><ref name="pmid32191623" />
*[[Thrombocytosis]] has been reported in 4% of patients with [[COVID-19]] infection.<ref name="pmid32007143">{{cite journal| author=Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y | display-authors=etal| title=Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. | journal=Lancet | year= 2020 | volume= 395 | issue= 10223 | pages= 507-513 | pmid=32007143 | doi=10.1016/S0140-6736(20)30211-7 | pmc=7135076 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32007143  }} </ref>


*<s>[[Leukocytosis]] is seen in 11.4% of patients with severe [[COVID-19]] infection compared to 4.8% of patients with non-severe infection.<ref name="pmid32109013" /><ref name="pmid32191623">{{cite journal| author=Lippi G, Plebani M| title=The critical role of laboratory medicine during coronavirus disease 2019 (COVID-19) and other viral outbreaks. | journal=Clin Chem Lab Med | year= 2020 | volume= 58 | issue= 7 | pages= 1063-1069 | pmid=32191623 | doi=10.1515/cclm-2020-0240 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32191623  }} </ref></s>
==Clinical Significance==
*<s>Increase in CRP is seen in 81.5% of patients with severe [[COVID-19]] infection compared to 56.4% of patients with non-severe infection.<ref name="pmid32109013" /><ref name="pmid32191623" /></s>
Laboratory findings in [[COVID-19]] infection may indicate clinical abnormalities, including:
*<s>Increase in [[procalcitonin]] is seen in 13.7% of patients with severe [[COVID-19]] infection compared to 3.7% of patients with non-severe infection.<ref name="pmid32109013" /><ref name="pmid32191623" /></s>
*<s>Increase in [[Aspartate transaminase|AST]] is seen in 39.4% of patients with severe [[COVID-19]] infection compared to 18.2% of patients with non-severe infection.<ref name="pmid32109013" /><ref name="pmid32191623" /></s>
*<s>Increase in [[ALT]] is seen in 28.1% of patients with severe [[COVID-19]] infection compared to 19.8%  of patients with non-severe infection.<ref name="pmid32109013" /><ref name="pmid32191623" /></s>
*<s>Increase in [[Lactate dehydrogenase|LDH]] is seen in 58.1% of patients with severe [[COVID-19]] infection compared to 37.2% of patients with non-severe infection.<ref name="pmid32109013" /><ref name="pmid32191623" /></s>
*<s>MDW was found to be increased in all patients with COVID-19 infection, particularly in those with the worst conditions.<ref name="pmid32191623" /></s>
*<s>Increase in total bilirubin is seen in 13.3% of patients with severe [[COVID-19]] infection compared to 9.9% of patients with non-severe infection.<ref name="pmid32109013" /><ref name="pmid32191623" /></s>
*<s>Increase in [[creatinine]] is seen in 4.3% of patients with severe [[COVID-19]] infection compared to 1% of patients with non-severe infection.<ref name="pmid32109013" /><ref name="pmid32191623" /></s>
*<s>[[Thrombocytosis]] has been reported in 4% of patients with [[COVID-19]] infection.<ref name="pmid32007143">{{cite journal| author=Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y | display-authors=etal| title=Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. | journal=Lancet | year= 2020 | volume= 395 | issue= 10223 | pages= 507-513 | pmid=32007143 | doi=10.1016/S0140-6736(20)30211-7 | pmc=7135076 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32007143  }} </ref></s>


==<s>Clinical Significance</s>==
*In patients with [[COVID-19]] infection, leukocytosis may be an indication of a bacterial infection or superinfection.<ref name="pmid32191623" />
<s>Laboratory findings in [[COVID-19]] infection may indicate clinical abnormalities, including:</s>
*In patients with [[COVID-19]] infection, increase in [[CRP]] may be an indication of severe viral infection or [[sepsis]] and [[viremia]].<ref name="pmid32191623" />
*In patients with [[COVID-19]] infection, increase in [[procalcitonin]] may be an indication of bacterial infection or [[superinfection]].<ref name="pmid32191623" />
*There have been different reports regarding the association of increase in [[ferritin]] with death in COVID-19 infection; for example, there has been a report that increase in [[ferritin]] is associated with [[Acute respiratory distress syndrome|acute respiratory distress syndrome (ARDS)]] but not death<ref name="pmid32167524">{{cite journal| author=Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S | display-authors=etal| title=Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. | journal=JAMA Intern Med | year= 2020 | volume=  | issue=  | pages=  | pmid=32167524 | doi=10.1001/jamainternmed.2020.0994 | pmc=7070509 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32167524  }} </ref>, while another one reports an association between increase in [[ferritin]] and death in COVID-19 infection<ref name="pmid32171076">{{cite journal| author=Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z | display-authors=etal| title=Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. | journal=Lancet | year= 2020 | volume= 395 | issue= 10229 | pages= 1054-1062 | pmid=32171076 | doi=10.1016/S0140-6736(20)30566-3 | pmc=7270627 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32171076  }} </ref>
*In patients with [[COVID-19]] infection, increase in [[aminotransferases]] may indicate injury to the [[liver]] or multi-system damage.<ref name="pmid32191623" />
*In patients with [[COVID-19]] infection, increase in [[aminotransferases]] may indicate injury to the liver or multi-system damage.<ref name="pmid32191623" />
*In patients with [[COVID-19]] infection, increase in [[Lactate dehydrogenase|LDH]] may indicate injury to the lungs or multi-system damage.<ref name="pmid32191623" />
*In patients with [[COVID-19]] infection, increase in total bilirubin may indicate injury to the liver.<ref name="pmid32191623" />
*In patients with [[COVID-19]] infection, increase in [[creatinine]] may indicate injury to the kidneys.<ref name="pmid32191623" />
*In patients with [[COVID-19]] infection, increase in cardiac troponins may indicate cardiac injury.<ref name="pmid32191623" />
*In patients with [[COVID-19]] infection, decrease in [[albumin]] may indicate liver function abnormality.<ref name="pmid32191623" />
*Increase in [[IL-6]] has been reported to be associated with death in  [[COVID-19]] infection.<ref name="pmid32167524" />


*<s>In patients with [[COVID-19]] infection, leukocytosis may be an indication of a bacterial infection or superinfection.<ref name="pmid32191623" /></s>
*<s>In patients with [[COVID-19]] infection, increase in [[CRP]] may be an indication of severe viral infection or [[sepsis]] and [[viremia]].<ref name="pmid32191623" /></s>
*<s>In patients with [[COVID-19]] infection, increase in [[procalcitonin]] may be an indication of bacterial infection or [[superinfection]].<ref name="pmid32191623" /></s>
*<s>There have been different reports regarding the association of increase in [[ferritin]] with death in COVID-19 infection; for example, there has been a report that increase in [[ferritin]] is associated with [[Acute respiratory distress syndrome|acute respiratory distress syndrome (ARDS)]] but not death<ref name="pmid32167524">{{cite journal| author=Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S | display-authors=etal| title=Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. | journal=JAMA Intern Med | year= 2020 | volume=  | issue=  | pages=  | pmid=32167524 | doi=10.1001/jamainternmed.2020.0994 | pmc=7070509 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32167524  }} </ref>, while another one reports an association between increase in [[ferritin]] and death in COVID-19 infection<ref name="pmid32171076">{{cite journal| author=Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z | display-authors=etal| title=Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. | journal=Lancet | year= 2020 | volume= 395 | issue= 10229 | pages= 1054-1062 | pmid=32171076 | doi=10.1016/S0140-6736(20)30566-3 | pmc=7270627 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32171076  }} </ref></s>
*<s>In patients with [[COVID-19]] infection, increase in [[aminotransferases]] may indicate injury to the [[liver]] or multi-system damage.<ref name="pmid32191623" /></s>
*<s>In patients with [[COVID-19]] infection, increase in [[aminotransferases]] may indicate injury to the liver or multi-system damage.<ref name="pmid32191623" /></s>
*<s>In patients with [[COVID-19]] infection, increase in [[Lactate dehydrogenase|LDH]] may indicate injury to the lungs or multi-system damage.<ref name="pmid32191623" /></s>
*<s>In patients with [[COVID-19]] infection, increase in total bilirubin may indicate injury to the liver.<ref name="pmid32191623" /></s>
*<s>In patients with [[COVID-19]] infection, increase in [[creatinine]] may indicate injury to the kidneys.<ref name="pmid32191623" /></s>
*<s>In patients with [[COVID-19]] infection, increase in cardiac troponins may indicate cardiac injury.<ref name="pmid32191623" /></s>
*<s>In patients with [[COVID-19]] infection, decrease in [[albumin]] may indicate liver function abnormality.<ref name="pmid32191623" /></s>
*<s>Increase in [[IL-6]] has been reported to be associated with death in  [[COVID-19]] infection.<ref name="pmid32167524" /></s>





Latest revision as of 08:38, 17 July 2020

Associate Editor(s)-in-Chief: Shakiba Hassanzadeh, MD[1]



Some Differential Diagnosis of Asperger Syndrome

(Modified Table from The Investigation and Differential Diagnosis of Asperger Syndrome in Adults)[1]

Asperger Syndrome Schizoid Personality Disorder Schizotypal Personality Disorder Avoidant Personality Disorder Social Phobia Obsessive Personality Disorder Obsessive-compulsive disorder (OCD) Attention deficit–hyperactivity disorder (ADHD)
Abnormal social interaction + + + + + + + +
Abnormal verbal communication + + + - - - - -
Abnormal facial expression/gestures/prosody + + + + +/-  - - +/- 
Abnormal eye contact + + +/-  + +/-  - - +/- 
Abnormal theory of mind + +/-  +/-  +/-  +/-  +/-  - +/- 
Abnormal empathy + +/-  +/-  - - +/-  - +/- 
Abnormal interests/rituals/compulsions + +/-  +/-  - - + + -
Abnormal attention +/-  - - - - - - +
Abnormal psychomotor function + - +/-  - - - - +/- 
Abnormal self-injurious behavior +/- +/-  +/-  - - - - +/- 
Abnormal psychotic manifestations +/- - +/-  - - - - -
Abnormal social interaction in childhood + +/-  +/-  +/-  - - - +
Abnormal biographical stress factors - + +/-  + +/-  + +/-  +/- 




Cytokine Storm

Cytokine storm is an immune reaction that is characterized by dysregulated and excessive release of proinflammatory cytokines.[2]

Cytokines Involved in Cytokine Storm

Pathogenesis of Cytokine Storm

  • Cytokine storm is an immune reaction that is characterized by dysregulated and excessive release of proinflammatory cytokines.[2]
  • During sepsis, cytokine storm may be the cause of tissue or organ injury.[3]
  • It has been suggested that the pathogenesis of severe COVID-19 infection may be due to cytokine storm and suppression of Th1 antiviral responses since the following findings have been reported to be associated with severe COVID-19 infection:[9][10]


Cytokines Involved in COVID-19-Associated-Cytokine Storm
Proinflammatory Interferones
  • IFN-γ
Interleukines
  • IL-1β
  • IL-6
Chemokines
  • CCL-2 (MCP-1)
  • CCL-3 (Macrophage inflammatory protein-1A)
  • CCL-5
  • IL-8 (CXCL8)
  • IP-10 (CXCL10)
Colony-stimulating

factors  

  • GM-CSF
Tumor necrosis

factor  

  • TNF-α
Anti-inflammatory Interleukines
  • IL-4
  • IL-10

Overview

COVID-19-Associated Hematologic Findings

Pathophysiology and Causes

Epidemiology

  • Leukocytosis is seen in 11.4% of patients with severe COVID-19 infection compared to 4.8% of patients with non-severe infection.[14][15]
  • Increase in CRP is seen in 81.5% of patients with severe COVID-19 infection compared to 56.4% of patients with non-severe infection.[14][15]
  • Increase in procalcitonin is seen in 13.7% of patients with severe COVID-19 infection compared to 3.7% of patients with non-severe infection.[14][15]
  • Increase in AST is seen in 39.4% of patients with severe COVID-19 infection compared to 18.2% of patients with non-severe infection.[14][15]
  • Increase in ALT is seen in 28.1% of patients with severe COVID-19 infection compared to 19.8% of patients with non-severe infection.[14][15]
  • Increase in LDH is seen in 58.1% of patients with severe COVID-19 infection compared to 37.2% of patients with non-severe infection.[14][15]
  • MDW was found to be increased in all patients with COVID-19 infection, particularly in those with the worst conditions.[15]
  • Increase in total bilirubin is seen in 13.3% of patients with severe COVID-19 infection compared to 9.9% of patients with non-severe infection.[14][15]
  • Increase in creatinine is seen in 4.3% of patients with severe COVID-19 infection compared to 1% of patients with non-severe infection.[14][15]
  • Thrombocytosis has been reported in 4% of patients with COVID-19 infection.[16]

Clinical Significance

Laboratory findings in COVID-19 infection may indicate clinical abnormalities, including:

  • In patients with COVID-19 infection, leukocytosis may be an indication of a bacterial infection or superinfection.[15]
  • In patients with COVID-19 infection, increase in CRP may be an indication of severe viral infection or sepsis and viremia.[15]
  • In patients with COVID-19 infection, increase in procalcitonin may be an indication of bacterial infection or superinfection.[15]
  • There have been different reports regarding the association of increase in ferritin with death in COVID-19 infection; for example, there has been a report that increase in ferritin is associated with acute respiratory distress syndrome (ARDS) but not death[17], while another one reports an association between increase in ferritin and death in COVID-19 infection[18]
  • In patients with COVID-19 infection, increase in aminotransferases may indicate injury to the liver or multi-system damage.[15]
  • In patients with COVID-19 infection, increase in aminotransferases may indicate injury to the liver or multi-system damage.[15]
  • In patients with COVID-19 infection, increase in LDH may indicate injury to the lungs or multi-system damage.[15]
  • In patients with COVID-19 infection, increase in total bilirubin may indicate injury to the liver.[15]
  • In patients with COVID-19 infection, increase in creatinine may indicate injury to the kidneys.[15]
  • In patients with COVID-19 infection, increase in cardiac troponins may indicate cardiac injury.[15]
  • In patients with COVID-19 infection, decrease in albumin may indicate liver function abnormality.[15]
  • Increase in IL-6 has been reported to be associated with death in COVID-19 infection.[17]



References

  1. 2.0 2.1 2.2 2.3 2.4 2.5 Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, Katze MG (2012). "Into the eye of the cytokine storm". Microbiol Mol Biol Rev. 76 (1): 16–32. doi:10.1128/MMBR.05015-11. PMC 3294426. PMID 22390970.
  2. Chousterman BG, Swirski FK, Weber GF (2017). "Cytokine storm and sepsis disease pathogenesis". Semin Immunopathol. 39 (5): 517–528. doi:10.1007/s00281-017-0639-8. PMID 28555385.
  3. Jiang Y, Xu J, Zhou C, Wu Z, Zhong S, Liu J; et al. (2005). "Characterization of cytokine/chemokine profiles of severe acute respiratory syndrome". Am J Respir Crit Care Med. 171 (8): 850–7. doi:10.1164/rccm.200407-857OC. PMID 15657466.
  4. Cameron MJ, Bermejo-Martin JF, Danesh A, Muller MP, Kelvin DJ (2008). "Human immunopathogenesis of severe acute respiratory syndrome (SARS)". Virus Res. 133 (1): 13–9. doi:10.1016/j.virusres.2007.02.014. PMC 7114310 Check |pmc= value (help). PMID 17374415.
  5. Reghunathan R, Jayapal M, Hsu LY, Chng HH, Tai D, Leung BP; et al. (2005). "Expression profile of immune response genes in patients with Severe Acute Respiratory Syndrome". BMC Immunol. 6: 2. doi:10.1186/1471-2172-6-2. PMC 546205. PMID 15655079.
  6. Ye Q, Wang B, Mao J (2020). "The pathogenesis and treatment of the `Cytokine Storm' in COVID-19". J Infect. 80 (6): 607–613. doi:10.1016/j.jinf.2020.03.037. PMC 7194613 Check |pmc= value (help). PMID 32283152 Check |pmid= value (help).
  7. Channappanavar R, Perlman S (2017). "Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology". Semin Immunopathol. 39 (5): 529–539. doi:10.1007/s00281-017-0629-x. PMC 7079893 Check |pmc= value (help). PMID 28466096.
  8. Liu J, Li S, Liu J, Liang B, Wang X, Wang H; et al. (2020). "Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients". EBioMedicine. 55: 102763. doi:10.1016/j.ebiom.2020.102763. PMC 7165294 Check |pmc= value (help). PMID 32361250 Check |pmid= value (help).
  9. Kuppalli K, Rasmussen AL (2020). "A glimpse into the eye of the COVID-19 cytokine storm". EBioMedicine. 55: 102789. doi:10.1016/j.ebiom.2020.102789. PMC 7204696 Check |pmc= value (help). PMID 32388462 Check |pmid= value (help).
  10. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y; et al. (2020). "Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China". Lancet. 395 (10223): 497–506. doi:10.1016/S0140-6736(20)30183-5. PMC 7159299 Check |pmc= value (help). PMID 31986264.
  11. 12.0 12.1 12.2 12.3 12.4 12.5 12.6 Frater JL, Zini G, d'Onofrio G, Rogers HJ (2020). "COVID-19 and the clinical hematology laboratory". Int J Lab Hematol. 42 Suppl 1: 11–18. doi:10.1111/ijlh.13229. PMC 7264622 Check |pmc= value (help). PMID 32311826 Check |pmid= value (help).
  12. Meisner M (2014). "Update on procalcitonin measurements". Ann Lab Med. 34 (4): 263–73. doi:10.3343/alm.2014.34.4.263. PMC 4071182. PMID 24982830.
  13. 14.0 14.1 14.2 14.3 14.4 14.5 14.6 14.7
  14. 15.00 15.01 15.02 15.03 15.04 15.05 15.06 15.07 15.08 15.09 15.10 15.11 15.12 15.13 15.14 15.15 15.16 15.17 15.18 Lippi G, Plebani M (2020). "The critical role of laboratory medicine during coronavirus disease 2019 (COVID-19) and other viral outbreaks". Clin Chem Lab Med. 58 (7): 1063–1069. doi:10.1515/cclm-2020-0240. PMID 32191623 Check |pmid= value (help).
  15. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y; et al. (2020). "Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study". Lancet. 395 (10223): 507–513. doi:10.1016/S0140-6736(20)30211-7. PMC 7135076 Check |pmc= value (help). PMID 32007143 Check |pmid= value (help).
  16. 17.0 17.1 Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S; et al. (2020). "Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China". JAMA Intern Med. doi:10.1001/jamainternmed.2020.0994. PMC 7070509 Check |pmc= value (help). PMID 32167524 Check |pmid= value (help).
  17. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z; et al. (2020). "Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study". Lancet. 395 (10229): 1054–1062. doi:10.1016/S0140-6736(20)30566-3. PMC 7270627 Check |pmc= value (help). PMID 32171076 Check |pmid= value (help).


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