During the course of the coronavirus disease 2019 (COVID-19) pandemic, reports of
a new
multisystem inflammatory syndrome in children (MIS-C) have been increasing in Europe
and
the United States (
1
–
3
). Clinical features in children
have varied but predominantly include shock, cardiac dysfunction, abdominal pain,
and
elevated inflammatory markers, including C-reactive protein (CRP), ferritin, D-dimer,
and interleukin-6 (
1
). Since June
2020, several case reports have described a similar syndrome in adults; this review
describes in detail nine patients reported to CDC, seven from published case reports,
and summarizes the findings in 11 patients described in three case series in
peer-reviewed journals (
4
–
6
). These 27 patients had cardiovascular,
gastrointestinal, dermatologic, and neurologic symptoms without severe respiratory
illness and concurrently received positive test results for SARS-CoV-2, the virus
that
causes COVID-19, by polymerase chain reaction (PCR) or antibody assays indicating
recent
infection. Reports of these patients highlight the recognition of an illness referred
to
here as multisystem inflammatory syndrome in adults (MIS-A), the heterogeneity of
clinical signs and symptoms, and the role for antibody testing in identifying similar
cases among adults. Clinicians and health departments should consider MIS-A in adults
with compatible signs and symptoms. These patients might not have positive SARS-CoV-2
PCR or antigen test results, and antibody testing might be needed to confirm previous
SARS-CoV-2 infection. Because of the temporal association between MIS-A and SARS-CoV-2
infections, interventions that prevent COVID-19 might prevent MIS-A. Further research
is
needed to understand the pathogenesis and long-term effects of this newly described
condition.
Potential MIS-A patients were identified from several sources: reports from clinicians
and health departments, published case reports, and published case series. Clinicians
and health departments in the United States voluntarily reported adult patients with
suspected MIS-A to CDC using the case report form*
developed for MIS-C after a Health Advisory was published on May 14, 2020, calling
for
reporting of MIS-C cases. The case report form included information on patient
demographics, underlying medical conditions, clinical findings, complications,
laboratory test results including those from SARS-CoV-2 testing, imaging findings,
treatments, and outcomes. Two clinician reviewers selected patients who fulfilled
the
working MIS-A case definition used in this report, which included the following five
criteria: 1) a severe illness requiring hospitalization in a person aged ≥21
years; 2) a positive test result for current or previous SARS-CoV-2 infection (nucleic
acid, antigen, or antibody) during admission or in the previous 12 weeks; 3) severe
dysfunction of one or more extrapulmonary organ systems (e.g., hypotension or shock,
cardiac dysfunction, arterial or venous thrombosis or thromboembolism, or acute liver
injury); 4) laboratory evidence of severe inflammation (e.g., elevated CRP, ferritin,
D-dimer, or interleukin-6); and 5) absence of severe respiratory illness (to exclude
patients in which inflammation and organ dysfunction might be attributable simply
to
tissue hypoxia). Patients with mild respiratory symptoms who met these criteria were
included. Patients were excluded if alternative diagnoses such as bacterial sepsis
were
identified.
To identify potential published cases, a literature search was performed on August
20,
2020, and 355 publications were identified.
†
Abstracts were screened by one reviewer to determine
whether cases met the working MIS-A case definition; when no abstract was available,
the
full paper was examined. The references were reviewed to identify additional relevant
articles. Data were obtained from published reports; authors were contacted to confirm
published data and, when necessary, to provide data not included in the original
articles.
Case Reports
Demographic characteristics and underlying conditions. Cases in nine
patients reported to CDC (Table 1) and seven
published case reports (Table 2), originating
from seven U.S. jurisdictions and the United Kingdom, met the working case
definition. The 16 patients ranged in age from 21 to 50 years and included seven men
and nine women. Five were reported as Hispanic, nine as African American, one as
Asian, and one as a United Kingdom–born man of African ethnicity. Nine
patients had no reported underlying medical conditions; six were obese, one had
poorly controlled diabetes mellitus type 2 (hemoglobin A1C >9.0%), two had
hypertension, and one had obstructive sleep apnea. Eight patients had documented
respiratory illness before developing symptoms of MIS-A, and eight did not.
TABLE 1
Demographics, clinical features, treatments, and outcomes of nine adults
reported to CDC with multisystem inflammatory syndrome (MIS) associated with
SARS-CoV-2 infection — United States, March–August
2020
Age (yrs), sex,
race/ethnicity, location
Underlying medical
conditions
Clinical signs and
symptoms
Previous respiratory
illness/SARS-CoV-2 testing
SARS-CoV-2 testing at
time of MIS-A admission
Laboratory studies
(peak)*
Imaging/Other diagnostic
studies
Treatments
Outcome and length of
stay
Patient 1: 27, female, African
American, Maine
None
Rigors, profuse diarrhea, diffuse rash x 5
days. Admitted with mixed shock (hypovolemic, vasoplegic,
cardiogenic) and acute renal failure.
No/Testing unknown
PCR (-), Ab (+)
CRP 344 mg/L; D-dimer 2818 ng/mL; ferritin
1082 ng/mL; troponin I 0.43 ng/mL; ALT 37 IU/L; ALC nadir 420
cells/μL
TTE: mild to moderate global hypokinesis,
left ventricular ejection fraction 45%, mildly dilated right
ventricle, mild tricuspid regurgitation, pericardial effusion.
CT chest: bilateral patchy ground-glass opacities, pleural
effusion.
CT abdomen/pelvis: abdominal free fluid.
Norepinephrine, vasopressin, midodrine,
heparin, corticosteroids
Discharged after 13 days
Patient 2: 50, male, African
American, Florida
None
Poor oral intake, chest pressure,
palpitations, diaphoresis x 3 days. Hemodynamically unstable on
admission.
No/Testing unknown
PCR (+), Ab (+)
CRP 84 mg/L; D-dimer 2310 ng/mL; ferritin
1919 ng/mL; troponin I 0.48 ng/mL; ALT 440 IU/L; ALC nadir 2500
cells/μL
EKG: atrial fibrillation/flutter with
rapid ventricular response, ST segment changes.
TTE:
ejection fraction 25%–30% with global hypokinesis.
CXR: small pleural effusions.
Remdesivir, corticosteroids
Discharged after 17 days
Patient 3: 46, male, African
American, Florida
Obesity, chronic right lower extremity
pain
Malaise, bilateral tinnitus, chest pain,
and vomiting x 4 days. Hypotensive and mildly hypoxemic on
admission.
Yes/Testing unknown
PCR (-), Ab (+)
CRP 217 mg/L; D-dimer 3790 ng/mL; ferritin
>100,000 ng/mL; troponin I 2.5 ng/mL; IL-6 1412 pg/mL; ALT
>10,000 IU/L; ALC nadir 400 cells/μL
EKG: ST-T segment changes.
CT
chest: dependent ground glass opacities.
CT abdomen: hepatic
steatosis.
Vasopressors, tocilizumab x 1,
heparin
Deceased
Patient 4: 21, male, African
American, Louisiana
Obesity
Fever, cough, nausea, vomiting,
lymphadenopathy x 6 days.
No/Testing unknown
PCR (-), Ab (+)
CRP 318 mg/L; D-dimer 1760 ng/mL; ferritin
4400 ng/mL; troponin T 0.65 ng/mL; IL-6 7 pg/mL; ATL 279 IU/L; ALC
nadir 700 cells/μL
TTE: severely decreased ejection fraction,
mild mitral regurgitation, right ventricular dysfunction, coronary
artery dilatation.
CT chest: ground glass opacities and
atelectasis.
ASA, corticosteroids, IVIG x 1
Discharged after 6 days
Patient 5: 33, male, African
American, Georgia
Obesity, HTN, depression
Fever, chest pain, abdominal pain,
diarrhea, dark urine x 4 days.
Yes/PCR (+) 41 days earlier
PCR (+), Ab (+)
CRP 182 mg/L; D-dimer 275 ng/mL; ferritin
375 ng/mL; troponin I 1.8 ng/mL; IL-6 74.3 pg/mL; ALT 30 IU/L; ALC
nadir 2070 cells/μL
CT chest: atelectasis.
CT
abdomen/pelvis: normal.
TTE: mitral and tricuspid
regurgitation.
Anticoagulation
Discharged after 5 days
Patient 6: 22, female, African
American, New York
None
Fever, chills, throat pain, odynophagia x
2 days.
No/Testing unknown
PCR (+), Ab (+)
CRP 355 mg/L; D-dimer 1882 ng/mL; ferritin
378 ng/mL; troponin T 0.06 ng/mL; IL-6 34.8 pg/mL; ALT 119 U/L; ALC
nadir 360 cells/μL
CT neck: retropharyngeal and
parapharyngeal edema.
EKG: intermittent complete heart block
with narrow junctional escape without hemodynamic compromise.
TTE: ejection fraction 50%.
CXR: dense bilateral
lower lobe air-space disease.
Phenylephrine, anticoagulation,
corticosteroids
Discharged after 19 days
Patient 7: 21, female, African
American, New York
Obesity
Fever, fatigue, throat and neck pain,
nausea, vomiting x 1 day.
Yes/PCR (+) 25 days earlier
PCR (+), Ab (+)
CRP 319 mg/L; D-dimer 713 ng/mL; ferritin
351 ng/mL; troponin T 0.04 ng/mL; IL-6 56.2 pg/mL; ALT 160 IU/L; ALC
nadir 260 cells/μL
CT neck: bilateral supraclavicular and
cervical lymphadenopathy with no discrete abscess or
collection.
CT chest: bilateral patchy ground-glass
opacities, pleural effusion.
TTE: mild to moderate diffuse
left ventricular hypokinesis. Mild to moderate decreased left
ventricular ejection fraction (40%). Small posterior pericardial
effusion. Mild tricuspid and mitral valve regurgitation.
Dobutamine, heparin, ASA x1,
corticosteroids x2
Discharged after 12 days
Patient 8: 47, female, African
American, New York
None
Weakness, sore throat, shortness of
breath, decreased exercise tolerance x 3 days.
Yes/Testing unknown
PCR (+), Ab testing not
performed
CRP 485 mg/L; D-dimer 1365 ng/mL; ferritin
948 ng/mL; troponin T 0.24 ng/mL; ALT 45 U/L; ALC nadir 1980
cells/μL
EKG: first degree AV block and nonspecific
T-wave abnormalities.
TTE: borderline left ventricular
ejection fraction (55%).
Heparin, convalescent plasma
Discharged after 8 days
Patient 9: 42, male, Asian,
New York
Obesity
Fever, shortness of breath, cough,
diarrhea, poor appetite, dysuria x 5 days.
Yes/PCR (+) 37 days earlier
PCR (-), Ab testing not performed
CRP 387 mg/L; D-dimer 3519 ng/mL; ferritin
7529 ng/mL; troponin T 0.60 ng/mL; ALT 66 U/L; ALC nadir 1740
cells/μL
TEE: mildly dilated left ventricle,
moderately dilated right ventricle, moderate biventricular
hypokinesis, moderately decreased left ventricular ejection fraction
(35%).
CXR: bilateral lower lobe opacities/airspace
disease.
Vasopressors, anticoagulation,
corticosteroids
Discharged after 9 days
Abbreviations: Ab = antibody;
ALC = absolute lymphocyte count; ALT = alanine
aminotransferase; ASA = aspirin;
CRP = C-reactive protein; CT = computed
tomography; CXR = chest radiograph;
EKG = electrocardiogram; HTN = hypertension;
IL-6 = interleukin-6; IVIG = intravenous
immunoglobulin; PCR = polymerase chain reaction; TEE =
transesophageal echocardiogram; TTE = transthoracic
echocardiogram.
* Normal ranges for laboratory studies: ALC 1000–4000
cells/μL; ALT 5–30 IU/L; CRP 0–10 mg/L; D-dimer <500
ng/mL; ferritin 12–300 ng/mL (men), 12–150 ng/mL (women); IL-6
≤1.8 pg/mL; troponin I <0.03 ng/mL; troponin T < 0.1 ng/mL.
TABLE 2
Demographics, clinical features, treatments, and outcomes of seven adults
reported in published literature with multisystem inflammatory syndrome
(MIS) associated with SARS-CoV-2 infection — United Kingdom and
United States, March–August 2020
Age (yrs), sex,
race/ethnicity, location
Underlying medical
conditions
Clinical
signs/symptoms
Previous respiratory
illness/SARS-CoV-2 testing
SARS-CoV-2 testing at
time of MIS-A admission
Laboratory studies
(peak)*
Imaging/Other diagnostic
studies
Treatments
Outcome and length of
stay
Patient 10†:
36, female, Hispanic, New York
None
Fever, abdominal pain, vomiting, and
diarrhea x 7 days; arthralgias and diffuse rash x 2 days. On
admission, nonexudative conjunctivitis, mucositis, edema of
bilateral hands and feet, palmar erythema, diffuse maculopapular
rash, and cervical lymphadenopathy.
No/Not tested
PCR (+), Ab (+)
CRP 300 mg/L; D-dimer 652 ng/mL; ferritin
684 ng/mL; troponin I 0.07 ng/mL; ALT 116 IU/L; ALC nadir 900
cells/μL
TTE: moderate tricuspid regurgitation,
pericardial effusion.
CT chest: right pleural effusion.
Ultrasound: gallbladder wall edema.
ASA, IVIG x1, corticosteroids
Discharged after 7 days
Patient 11§:
45, male, Hispanic, New York
None
Fever, sore throat, diarrhea, lower
extremity pain, and diffuse rash x 6 days. On admission, hypotensive
and tachycardic with nonexudative conjunctivitis, periorbital edema,
mucositis, unilateral cervical lymphadenopathy, and diffuse
exanthem.
No/Not tested
PCR (+), Ab testing not
performed
CRP 547 mg/L; D-dimer 2977 ng/mL; ferritin
21,196 ng/mL; troponin 8.1 ng/mL; IL-6 117 pg/mL; ALT 133 IU/L; ALC
nadir 700 cells/μL
EKG: ST elevations in anterolateral leads.
TTE: ejection fraction 40% with global hypokinesis.
CT head/neck: pre-septal edema. Slit lamp:
uveitis.
Heparin, corticosteroids, IVIG x 2,
Tocilizumab x 1
Discharged after 9 days
Patient 12¶:
44, female, Hispanic, Massachusetts
GERD, mild obstructive sleep apnea,
depression
Chills, sore throat, cough, myalgias x 2
days (8 days before admission); followed by diarrhea and back pain x
3 days; followed by pleuritic chest pain and dyspnea. Admitted with
profound cardiogenic shock.
Yes/Not tested
PCR (+), Ab testing not
performed
CRP 141 mg/L; D-dimer 8691 ng/mL; ferritin
2564 ng/mL; hs-Trop T 1810 ng/L; IL-6 53.3 pg/mL; ALT 242 IU/L; ALC
nadir 670 cells/μL
EKG: submillimeter ST-segment elevation in
leads I/aVL, low QRS voltage.
TTE: severely depressed left
ventricular function, trace pericardial effusion.
CT chest:
mild ground glass opacities bilateral lung fields.
CT
abdomen/pelvis: small amount of ascites, periportal edema.
Norepinephrine, dobutamine, vasopressin,
milrinone, IVIG x 5 days, ECMO to LVAD and RVAD.
Discharged to rehabilitation facility
after 18 days; home 7 days later
Patient 13**: 21, male,
African origin, United Kingdom
None
Fever, headache, and abdominal pain x 6
days; transient palmar rash. Hypotensive on admission with
nonexudative conjunctivitis, mucositis,
cervicallymphadenopathy.
No/Not tested
PCR (-), Ab (+)
CRP 338 mg/L; D-dimer 4260 ng/mL; ferritin
1249 ng/mL; troponin T 3.3 ng/mL; ALT 330 IU/L; ALC nadir 390
cells/μL
CT abdomen/pelvis: mesenteric adenopathy
and ileitis.
EKG: sinus tachycardia.
CT chest:
normal.
TTE: normal.
CT coronary angiogram:
normal.
ASA, corticosteroids, IVIG x 1
Discharged after 8 days
Patient
14††: 31, female, African American,
Louisiana
Obesity, HTN, diabetes mellitus type
2
Fever x 1 day, throbbing neck pain,
nausea, vomiting.
Yes/PCR (+) 14 days before
admission
PCR (-), Ab testing not
performed
CRP 580 mg/L; D-dimer 453 ng/mL; ferritin
793 ng/mL; ALT 52 IU/L; ALC nadir 2120 cells/μL
Pathology: small-vessel cardiac
vasculitis; new pulmonary thrombi in a background of otherwise
reparative changes in the lungs.
CT head/neck: bilateral
enlarged parotid glands.
CT chest: interval improvement of
bibasilar ground-glass opacities with cervical and anterior
mediastinal lymphadenopathy.
CPR
Deceased at admission (ventricular
fibrillation)
Patient
15§§: 25, female, Hispanic,
Georgia
None
Fever, weakness, and shortness of breath x
7 days; followed by sore throat, mild cough, vomiting, and diarrhea.
Hypotensive on admission with conjunctivitis, mucositis, cervical
lymphadenopathy.
No/Not tested
PCR (+), Ab (+)
CRP 90 mg/L; D-dimer 1918 ng/mL; ferritin
798 ng/mL; troponin I 0.06 ng/mL; ALT 25 IU/L, ALC nadir 1150
cells/μL
TTE: moderate to severely reduced
right-sided ventricular dysfunction, flattened interventricular
septum in systole consistent with right ventricular pressure
overload.
EKG: right axis deviation.
CT chest:
scattered patchy ground glass opacities and peripheral
consolidation, small bilateral pleural effusions with adjacent
atelectasis; mild enlargement of the main pulmonary artery without
pulmonary embolus.
CT abdomen/ pelvis: mild peripancreatic
fat stranding, nonspecific bilateral perinephric fat
stranding.
ASA, IVIG x 2, vasopressors
Discharged after 5 days
Patient
16¶¶: 38, female, Hispanic, Texas
None
Fever, occipital headache, conjunctival
injection, odynophagia, mucositis, glossitis shortness of breath,
vomiting, polyarthralgia, and rash x 5 days.
Yes/PCR (+) 28 days earlier
PCR (+), Ab (+)
CRP 217 mg/L; D-dimer 1250 ng/mL; ferritin
196 ng/mL; troponin I <0.03 ng/mL; ALT 126 IU/L; ALC nadir 120
cells/μL
TTE: trace pericardial effusion, elevated
pulmonary artery pressure (46–51 mmHg), normal left
ventricular ejection fraction, no coronary artery
abnormalities.
CT chest/abdomen/pelvis: no pulmonary emboli,
right upper lobe perihilar ground-glass opacities, septal and
bronchial wall thickening, bilateral small-to-moderate pleural
effusions.
ASA,
corticosteroids, IVIG x
2
Discharged after 7 days
Abbreviations: Ab = antibody;
ALC = absolute lymphocyte count; ALT = alanine
aminotransferase; ASA = aspirin;
CPR = cardiopulmonary resuscitation;
CRP = C-reactive protein; CT = computed
tomography; ECMO = extracorporeal membrane oxygenation;
EKG = electrocardiogram; GERD = gastroesophageal
reflux disease; hs-Trop T = high sensitivity troponin T;
HTN = hypertension; IL-6 = interleukin-6;
IVIG = intravenous immunoglobulin; LVAD = left
ventricular assist device; PCR = polymerase chain reaction;
RVAD = right ventricular assist device;
TTE = transthoracic echocardiogram.
* Normal ranges for laboratory studies: ALC 1000–4000 cells/μL;
ALT 5–30 IU/L; CRP 0–10 mg/L; D-dimer <500 ng/mL; Ferritin
12–300 ng/mL (men), 12–150 ng/mL (women); hs-Trop T 0–9
ng/L IL-6 ≤1.8 pg/mL; troponin I <0.03 ng/mL; troponin T < 0.1
ng/mL.
†
https://www.sciencedirect.com/science/article/pii/S0735675720305428?via%3Dihub.
§
https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(20)31526-9.pdf.
¶
https://www.nejm.org/doi/10.1056/NEJMcpc2004975.
** https://www.sciencedirect.com/science/article/pii/S2665991320302344?via%3Dihub.
††
https://www.acpjournals.org/doi/10.7326/L20-0882.
§§
https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-020-05439-z.
¶¶
https://ard.bmj.com/content/early/2020/09/25/annrheumdis-2020-218959.
Initial signs and symptoms. Twelve of 16 patients had fever
(≥100.4°F [38.0°C] for ≥24 hours or report of subjective
fever lasting ≥24 hours) at the time of presentation. Six patients were
initially evaluated for possible cardiac symptoms such as chest pain or
palpitations; all 16 had evidence of cardiac effects, including electrocardiogram
abnormalities such as arrhythmias, elevated troponin levels, or echocardiographic
evidence of left or right ventricular dysfunction. Thirteen patients had
gastrointestinal symptoms on admission; five had dermatologic manifestations on
admission, including three with mucositis. Despite minimal respiratory symptoms, 10
patients had pulmonary ground glass opacities, and six had pleural effusions
identified on chest imaging.
Inflammatory markers. All patients had markedly elevated laboratory
markers of inflammation, including CRP (range of peak
values = 84–580 mg/L; upper limit of normal
[ULN] = 10 mg/L) and ferritin (196 to >100,000 ng/mL;
ULN = 150 ng/mL for women, 300 ng/mL for men), as well as markers of
coagulopathy including D-dimer (275–8691 ng/mL; ULN = 500 ng/mL). Ten
patients had absolute lymphocyte counts lower than normal range (range of nadir
values 120–2120 cells/μL; lower limit of normal = 1000
cells/μL).
SARS-CoV-2 test results. Ten patients received positive SARS-CoV-2 PCR
test results at the time of initial assessment for MIS-A, seven of whom also had
serologic evidence of infection (positive antibody test results) at that time. Six
patients received negative SARS-CoV-2 PCR test results; of those, four had positive
anti-SARS-CoV-2 antibody test results when first evaluated. Two patients had
positive SARS-CoV-2 PCR test results 14 and 37 days before admission, negative PCR
results at the time of admission, and no known antibody testing. Three additional
patients had positive SARS-CoV-2 PCR test results 25–41 days before admission
and continued positive PCR test results at the time of admission.
Treatment. Seven patients were treated with intravenous immunoglobulin,
10 with corticosteroids, and two with the interleukin-6 inhibitor, tocilizumab. Ten
patients required intensive care; seven required inotropes or vasopressors, and one
required mechanical circulatory support (extracorporeal membrane oxygenation
followed by temporary left and right ventricular assist devices). Three patients
required endotracheal intubation and mechanical ventilation, and two patients
died.
Published Case Series
Three published case series were identified describing adult patients with
manifestations consistent with MIS-A (
4
–
6
). One series describes seven previously healthy,
young adult men aged 20–42 years who experienced mixed cardiogenic and
vasoplegic shock and hyperinflammation along with high SARS-CoV-2 immunoglobulin G
antibody titers indicating active or previous infection (
4
). Two of the patients identified as African
American, two as Hispanic, two as Middle Eastern, and one as White. Four of the
seven patients had negative PCR test results for SARS-CoV-2 at the time of
admission, all had markedly elevated inflammatory markers and required inotropes or
vasopressors, and three required intraaortic balloon pumps. All were treated with
corticosteroids and therapeutic anticoagulation. All seven patients recovered and
were discharged home after 7 to 18 days of hospitalization with improved
cardiovascular function.
A second case series describes two patients aged 21 and 50 years who came to medical
attention because of large-vessel strokes associated with positive SARS-CoV-2 tests
(
5
). Information on
race/ethnicity of these patients was not reported. These patients had elevated
inflammatory markers and minimal respiratory symptoms, consistent with MIS-A. The
authors proposed endothelial dysfunction and coagulopathy related to SARS-CoV-2
infection as potential etiologies. Incidence of large-vessel stroke among young
adults during this same time the previous year was statistically significantly lower
(
5
).
A third case series describes the pathologic findings of endothelialitis and
complement deposition in the vessels of two patients with illness resembling MIS-A
(cardiac dysfunction, abdominal signs and symptoms, and rash) associated with
positive SARS-CoV-2 test results (
6
). Information on race/ethnicity of these patients was
not reported. One of these two patients had no underlying medical conditions and
recovered; the other had multiple underlying conditions at higher risk for severe
COVID-19 and died hours after seeking care. Pathologic findings in this case series
were similar to autopsy findings for those of patient 14 (Table 2).
Discussion
Findings indicate that adult patients of all ages with current or previous SARS-CoV-2
infection can develop a hyperinflammatory syndrome resembling MIS-C. Although
hyperinflammation and extrapulmonary organ dysfunction have been described in
hospitalized adults with severe COVID-19, these conditions are generally accompanied
by respiratory failure (
7
).
In contrast, the patients described here had minimal respiratory symptoms,
hypoxemia, or radiographic abnormalities in accordance with the working case
definition, which was meant to distinguish MIS-A from severe COVID-19; only eight
of
16 patients had any documented respiratory symptoms before onset of MIS-A.
The pathophysiology of MIS in both children and adults is currently unknown. Eight
of
27 (30%) adults described in this report and 45% of 440 children with MIS-C reported
to CDC through July 29, 2020, (
1
) had negative PCR and positive SARS-CoV-2 antibody
test results, suggesting MIS-A and MIS-C might represent postinfectious processes.
However, in some patients, persistent infection outside the upper respiratory tract
is possible; SARS-CoV-2 has been identified in multiple organs including the heart,
liver, brain, kidneys, and gastrointestinal tract (
7
). Additional proposed mechanisms for
extrapulmonary dysfunction in COVID-19 include endothelial damage and
thromboinflammation, dysregulated immune responses, and dysregulation of the
renin-angiotensin-aldosterone system (
7
).
The interval between infection and development of MIS-A is unclear, adding to
uncertainty regarding whether MIS-A represents a manifestation of acute infection
or
an entirely postacute phenomenon. In patients with COVID-19, dyspnea is typically
experienced a median of 5–8 days and critical illness 10–12 days after
onset of symptoms.
§
In
patients who reported typical COVID-19 symptoms before MIS-A onset, MIS-A was
experienced approximately 2–5 weeks later. However, eight MIS-A patients
reported no preceding respiratory symptoms, making it difficult to estimate when
initial infection occurred.
Given the high proportion of MIS-C patients with negative PCR testing, clinical
guidelines recommend the use of both antibody and viral testing to assist with
diagnosis (
8
–
10
). In patients with atypical
or late manifestations of SARS-CoV-2 infection, including MIS-A, positive antibody
results might be crucial to augment clinical recognition of this condition and guide
treatment. In addition, the use of a panel of laboratory tests for inflammation,
hypercoagulability, and organ damage (e.g., CRP, ferritin, D-dimer, cardiac enzymes,
liver enzymes, and creatinine) might assist in the early identification and
management of this COVID-19–associated condition.
All but one of the patients with MIS-A described in this report belonged to racial
or
ethnic minority groups. Long-standing health and social inequities have resulted in
increased risk for infection and severe outcomes from COVID-19 in communities of
color.¶ MIS-C has also been reported disproportionately in
these communities (1). Because patients described in this review
represent a convenience sample from a small number of jurisdictions, conclusions
cannot be made regarding the true burden or determinants of MIS-A in different
groups; further research is needed.
The majority (24 of 27) of patients with MIS-A survived, similar to those with MIS-C,
associated with receiving care in acute, often intensive, health care settings.
Because of the potential therapies that might benefit these patients as described
in
these case reports, clinicians should consider MIS-A within a broader differential
diagnosis when caring for adult patients with clinical and laboratory findings
consistent with the working MIS-A case definition.
The findings in this report are subject to at least three limitations. First, cases
described here were voluntarily reported or published and therefore are not
representative of the true clinical spectrum or racial/ethnic distribution of this
emerging syndrome. Additional cases might not have been reported or published;
others might have remained unrecognized because of absence of COVID-like symptoms,
lack of antibody testing, or negative test results. Second, the working case
definition excludes patients with severe respiratory dysfunction to distinguish
MIS-A from severe COVID-19; however, the two conditions might overlap in some cases.
Finally, the working case definition for this syndrome is potentially nonspecific,
and some patients with other disease processes might have been misclassified as
having MIS-A.
Clinicians and health departments should consider MIS-A in adults with signs and
symptoms compatible with the current working MIS-A case definition. Antibody testing
for SARS-CoV-2 might be needed to confirm previous COVID-19 infection in patients
who do not have positive SARS-CoV-2 PCR or antigen test results. Findings in this
convenience sample emphasize the importance of collecting race/ethnicity data on
case reports at the jurisdictional level. As with children, it is important that
multidisciplinary care be considered to ensure optimal treatment. In the process of
learning more from MIS-A cases, the working case definition might need to be revised
in order to systematically conduct a call for cases. Further research is needed to
understand the pathogenesis and long-term effects of this newly described condition.
Ultimately, the recognition of MIS-A reinforces the need for prevention efforts to
limit spread of SARS-CoV-2.
Summary
What is already known about this topic?
Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe
complication of SARS-CoV-2 infection in children and adolescents. Since June
2020, several case reports and series have been published reporting a
similar multisystem inflammatory syndrome in adults (MIS-A).
What is added by this report?
Cases reported to CDC and published case reports and series identify MIS-A in
adults, who usually require intensive care and can have fatal outcomes.
Antibody testing was required to identify SARS-CoV-2 infection in
approximately one third of 27 cases.
What are the implications for public health practice?
Clinical suspicion and indicated SARS-CoV-2 testing, including antibody
testing, might be needed to recognize and treat adults with MIS-A. Further
research is needed to understand the pathogenesis and long-term effects of
this condition. Ultimately, the recognition of MIS-A reinforces the need for
prevention efforts to limit spread of SARS-CoV-2.