Hematologic autoimmune disorders in the course of COVID-19: a systematic review of reported cases

Figures & data

Figure 1. PRISMA flowchart of the current systematic review process.

Table 1. Autoimmune hematologic complications of SARS-CoV-2 infections.

First author	History of the patient	Clinical presentations	Timing of the hematologic presentations	Autoimmune disorder	Treatment	Outcome
Zagorski et al. [16]	A 46 Y/O female K/C of iron deficiency anemia, asthma, splenectomy and ITP 27 years ago during pregnancy	Fever, dyspnea, muscle aches, lethargy, ill with generalized jaundice, increased work of breathing, no petechiae or rash	Not mentioned	AIHA –cold agglutinin syndrome	–	Deceased within hours of admission
Patil et al. [17]	51 Y/O female K/C of breast ductal carcinoma in situ post-mastectomy on chemoradiation	Fever, dyspnoea, malaise, pain of ribs and back, tachycardia, O2 sat: 88%	Not mentioned	AIHA – cold agglutinin syndrome	HCQ, solumedrol, heparin, folic acid, packed cell transfusion, warm IV fluids	Recovered (Hb became stable at day 2 and patient discharged after more than 4 days)
Capes et al. [18]	62 Y/O smoker male K/C of HTN and oropharyngeal squamous cell carcinoma on chemoradiation	Fever, mild dyspnea with low O2 sat, marked asthenia Acrocyanosis on day 16 of admission	About 1–2 weeks	AIHA – cold agglutinin syndrome	Packed cell transfusion	Recovered (at 6-week follow-up, the patient was slowly recovering from respiratory failure)
Moonla et al. [19]	24 Y/O female	Fever, dyspnea, dry cough	About 3 days	AIHA – cold agglutinin syndrome	HCQ, darunavir/ritonavir azithromycin, favipiravir	Recovered (Hb starts to raise after 2 days and her respiratory condition recovered in 2 weeks)
Maslov et al. [20]	48 Y/O male K/C of essential HTN, T1DM, obesity and end-stage renal disease on peritoneal dialysis	A weeklong history of weakness, anosmia and decreased appetite, O2 sat: 100% After 3 h of admission, his neurological status declined and he was intubated for airway protection and became hypotensive	Not mentioned	AIHA – cold agglutinin syndrome	Packed cell transfusion	Deceased within 48 h after admission
Jensen et al. [21]	1. 70 Y/O male 2. 67 Y/O male	1. Fever, cough, hypoxia 2. Dyspnea	1. More than 2 days 2. Not mentioned	AIHA – cold agglutinin syndrome	1. HCQ, Ceftriaxone, heparin infusion, vasopressors 2. HCQ, Azithromycin, ceftriaxone	1. Complicated course (not much detail on recovery course) 2. Deceased
Huscenot et al. [12]	1. 43 Y/O obese female K/C of untreated multiple sclerosis 2. 63 Y/O male K/C of HTN	1. Fever, dyspnea, cough, diarrhea, asthenia 2. Fever, progressive worsening dyspnea, cough	1. 16 days 2. 20 days	AIHA – cold agglutinin syndrome	1. Ceftriaxone, tazocilline, azithromycin, packed cell transfusion 2. Not mentioned	1. Recovered (Hb started to raise after 1 d) 2. Recovered (Hb started to raise after 1 d and patient discharged on day 15)
Lazarian et al. [22]	1. 61 Y/O male K/C of HTN and CKD 2. 89 Y/O female K/C of HTN, CKD and AF 3. 62 Y/O male K/C of HTN and cirrhosis 4. 69 Y/O obese female 5. 61 Y/O male K/C of HTN, CKD, DM and hypercholesterolemia 6. 61 Y/O male K/C of DM 7. 75 Y/O obese male K/C of cardiopathy, obstructive bronchopneumopathy, hypercholesterolemia	Not mentioned	1. 13 days 2. 7 days 3. 4 days 4. 10 days 5. 11 days 6. 9 days 7. 6 days	AIHA	1. Steroid 2. Steroid 3. Steroid, rituximab 4. Steroid 5. Packed cell 6. Steroid, rituximab 7. Packed cell	1. Recovered 2. Recovered 3. Recovered 4. Recovered 5. Recovered 6. Recovered (failure with steroid and ongoing with rituximab 7. Recovered
Lopez et al. [23]	46 Y/O female K/C of congenital thrombocytopenia not on therapy	Fever, dyspnea, progressive cough, tachycardia, O2 sat: 99%	About 3 days	Warm AIHA	HCQ, patient failed to respond to IVIG but had good response to steroid, packed cell transfusion	Recovered (Hb raised on days 3 of admission after change of IVIG to steroid and patient discharged on day 8)
Hindilerden et al. [11]	56 Y/O male K/C of HTN	Dyspnea, cough, headache, loss of smell, progressive fatigue, jaundice, tachycardia, tachypnea	4 days	AIHA	Favipiravir, patient failed to respond to IVIG but had good response to steroid, packed cell transfusion	Recovered (patient was completely transfusion independent and symptom-free with the resolution of his pneumonia after 8 days of steroid and discharged on day 14)
Jacobs et al. [24]	33 Y/O female K/C of hypothyroidism	Headache for 2 days and family concern for altered mental status, confused, scleral icterus, tachycardia, tachypnea, delayed responses upon questioning and sluggish reactions to verbal commands	Not mentioned	AIHA	Tocilizumab on day 6, steroid, rituximab on day 10, packed cell transfusion	Recovered (Hb raised shortly after steroid administration on day 1 but the level was unstable; following rituximab therapy, Hb began to stabilize and patient was discharged on day 13)
Hernández et al. [25]	Patient K/C of psoriasis	7-day period of fever, asthenia, headache and a syncope episode without loss of consciousness, tachycardia with hemodynamic stability and mucocutaneous pallor	7 days	AIHA	Steroid	Recovered (Hb raised after steroid administration complete recovery of Hb occurred after 2 weeks)
Jawed et al. [26]	In early 50s Y/O male K/C of uncontrolled HTN and obstructive sleep apnea	Coryzal symptoms 2 weeks prior, shortness of breath on mild exertion, diarrhea, mild jaundice yellowish discoloration of eyes, dark urine, an episode of frank per rectum bleeding, high blood pressure, O2 sat: 96%	About 14 days	AIHA	Adenosine (for supraventricular tachycardia), bisoprolol	Recovered (patient discharged on day 33)
D’Aloisio et al. [27]	46 Y/O male K/C of HTN and hereditary spherocytosis	Respiratory failure and unilateral visual loss after a 12-day history of fever, worsening dyspnea and cough Ophthalmoscopy: bilateral retinal hemorrhage with macular involvement	12 days	AIHA- Cold agglutinin syndrome	Chloroquine, packed cell transfusion	Recovered (patient discharged on day 13)
Sereno et al. [28]	58 Y/O smoker male K/C of advanced small cell lung cancer	Fever, cough, chest pain, progressive asthenia, tachypnea	2 days	Possible autoimmune neutropenia due to coronavirus	HCQ, meropenem, dexamethasone, granulocyte colony-stimulating factor	Recovered (respiratory symptoms improved within 3 days and patient discharged on day 15)
Wahlster et al. [29]	17 Y/O male K/C of refractory chronic ITP on eltrombopag and mycophenolate mofetil	Fever, fatigue, emesis, diarrhea, progressive jaundice, marked pallor, tachycardia, tachypnea and hypoxemia	4 days	Evans syndrome	Steroid, packed cell transfusion	Recovered (Hb became stable within 48 h of steroid administration)
Li et al. [30]	39 Y/O male	First admission: fever, chills, dyspnea, hemoptysis, epistaxis, sore throat, productive cough, tachycardia, tachypnea, oral blood blister, hematemesis, melena, hematochezia and no petechiae, ecchymosis or rash Second admission (10 days later, 4 days after first discharge): intermittent fever, cough, extreme weakness, fatigue and no bleeding	About 7 days	Evans syndrome	First admission: proton pump inhibitor, IVIG Second admission: IVIG	Recovered (in first admission that patient had ITP, resolution of bleeding and raise of Plt occurred on day 5 and the patient was discharged on day 6; Hb drop also responded to IVIG in second admission)
Vadlamudi et al. [31]	23 Y/O female gravida 2, para 1, at 38 weeks of pregnancy in active labor	Spontaneous rupture of membranes, contractions, blood-tinged discharge, history of ecchymosis and an episode of epistaxis 2 weeks prior, no pallor, ecchymosis or organomegaly On day 38 of postpartum: chest pain and shortness of breath	Not clear	Evans syndrome	IV iron dextran, IVIG, rituximab, dexamethasone, packed cell and Plt transfusion	Recovered
Zulfiqar et al. [9]	65 Y/O woman K/C of HTN and autoimmune hypothyroidism	On admission: fever, dry cough, fatigue, abdominal discomfort, tachypnea, O2 sat: 89% On day 4: epistaxis and lower extremity purpura On day 9: right frontal headache without fever, vomiting or focal neurologic deficit	8 days	ITP	IV amoxicillin–clavulanic acid, Plt failed to raise in response to IVIG but increased in response to steroid and eltrombopag, Plt transfusion	Recovered (after administration of steroid and eltrombopag at day 9, Plt increase at day 10 and purpura resolved at day 13)
Revuz et al. [32]	1. 57 Y/O female K/C of psoriatic arthritis on adalimumab and methotrexate 2. 76 Y/O male K/C of metastatic bronchiolar adenocarcinoma on carboplatin, pemetrexed and pembrolizumab 3. 39 Y/O male with history of ITP 15 years ago	1. Fever, tachypnea, petechiae on legs and gingival mucosa 2. Fever, slight purpura on legs 3. Fever, cough, arthralgia, body aches, unilateral epistaxis	1. 9 days 2. The lowest Plt at day 11 3. Less than 7 days	ITP	1. IVIG 2. IVIG 3. IVIG	1. Recovered (Plt raised after first dose of IVIG) 2. Recovered (Plt returned to normal in 7 days) 3. Recovered (Plt raised significantly after first dose of IVIG)
Bennett et al. [33]	73 Y/O female K/C of HTN, hyperlipidemia, seasonal allergies	Fever, shortness of breath, headache, fatigue, diarrhea, generalized body aches	Less than 7 days	ITP	HCQ, dexamethasone (without response), IVIG, Plt transfusion	Recovered (Plt had marked response to treatment on day 4 and discharged on day 5)
Bomhof et al. [34]	1. 59 Y/O male K/C of small bowel stage IV neuroendocrine tumor 2. 66 Y/O female K/C of HTN 3. 67 Y/O male K/C of HTN and DM	1. History of cough and fever 10 days before, oral petechiae and skin hematomas 2. History of fever, dyspnea, cough, diarrhea and vomiting 4 weeks ago, petechiae, epistaxis, increased hemorrhoid blood loss 3. Fever, dyspnea, cough	1. 10 days 2. About 4 weeks 3. 21 days	ITP	1. IVIG, dexamethasone, Plt transfusion 2. Patient did not respond to dexamethasone but responded to IVIG, Plt transfusion 3. Plt transfusion	1. Recovered (Plt raised rapidly in response to IVIG but dropped again, then dexamethasone was administrated and significantly increased Plt) 2. Recovered (Plt raised in response to IVIG administration at day 6) 3. Deceased within 24 h of ITP occurrence (due to intracerebral bleeding)
Hindilerden et al. [35]	86 Y/O male K/C of HTN and DM	Fever, dry cough, fatigue, excessive purpuric eruptions and bruising, oral hemorrhagic bullae, tachycardia, O2 sat: 91%	<7 days	ITP	Favipiravir, azithromycin, IVIG, prednisolone	Recovered (Plt responded to treatment and doubled in 2 days and normalized in the 3rd week)
Lorenzo-Villalba1 et al. [36]	1. 66 Y/O male K/C of HTN, DM & liver cirrhosis 2. 57 Y/O female K/C of HTN, thyroidectomy & secondary hypoparathyroidism 3. 79 Y/O male K/C of HTN and a previous episode of transient recovered pancytopenia	1. Fever, progressive shortness of breath, cough, diarrhea, tachycardia, O2 sat: 93%, diminished Breath sounds with rales in left side, facial and trunk erythema, epistaxis 2. Fever, progressive shortness of breath, dry cough, epistaxis, cutaneous purpura on the lower extremities, oral hemorrhagic bubbles, tachycardia, O2 sat: 92%, diminished Breath sounds with rales in left side 3. Fever, dry cough, confusion, falls, cutaneous petechial purpura on the lower limbs, O2 sat: 93%, diminished breath sound with rales in the right pulmonary base	1. 11 days 2. 8 days 3. About 7 days	1. ITP	1. IVIG, eltrombopag 2. IVIG, eltrombopag 3. No IVIG or eltrombopag	1. Recovered (IVIG was discontinued owing to acute heart failure. Eltrombopag then initiated and after 3 days Plt increased and patient discharged on day 15) 2. Recovered (patient was discharged on day 14) 3. Recovered (spontaneously)
Deruelle et al. [37]	41 Y/O obese man K/C of HTN	Fever, dyspnea, cough, tachypnea, O2 sat: 97%	13 days	ITP	Steroid, IVIG	Recovered (IVIG were introduced on day 14 and Plt began rising after 3 days and then fell again on day 19. IVIG was then administered and 2 days later, Plt returned to normal)
Lévesque et al. [38]	53 Y/O male K/C of HTN, DM, dyslipidemia	Abnormal bleeding from the tracheotomy site and the left main stem bronchus during tracheotomy, no skin purpura	20 days	ITP	Antibiotic combination, IVIG, Plt did not rise in response to high-dose dexamethasone and intravenous tranexamic acid but responded to romiplostim and vincristine, packed cell and Plt transfusion	Recovered (the bleeding finally stopped with the high platelet transfusion support within first 5 days but Plt did not rise; Plt started to increase after 6 days of romiplostim)
Merli et al. [39]	37 Y/O female K/C of SLE and chronic ITP secondary to lupus (treated with IVIG)	History of fever, dry cough, anosmia and fatigue 14 days ago, sudden appearance of lower extremities purpura	14 days	ITP	HCQ, lopinavir/ritonavir, methylprednisolone, IVIG	Recovered (Plt gradually increased and the patient was discharged on day 11)
Yang et al. [40]	1. 32 Y/O female 2. 65 Y/O female K/C of HTN and autoimmune hypothyroidism	1. Fever, cough, fatigue, skin petechia mainly on lower extremities 2. Fever, cough, fatigue, abdominal discomfort, tachypnea, O2 sat: 89	1. 13 days 2. 9 days	ITP	1. Lianhua, qingwen, oseltamivir, methylprednisolone, Plt transfusion 2. Steroid, IVIG	1. Recovered (not much detail on recovery course) 2. Unknown
Martincic et al. [41]	48 Y/O obese male K/C of T2DM and obstructive sleep apnea	Fever, progressive dyspnea, cough, headache, muscle soreness, tachycardia, tachypnea, O2 sat: 60% while receiving high flow oxygen via a non-rebreather mask, blood pressure: 163/60 On day 9: macroscopic hematuria, minor bleeding from oral mucosa and blood clots in gastric residual volume On day 12: petechial bleeding on the torso	12 days	ITP	HCQ, lopinavir/ritonavir, tazocin, nadroparin, IVIG, dexamethasone, pooled Plt concentrate transfusion	Recovered (Plt normalized within 3 days and patient discharged on day 23)
Humbert et al. [42]	84 Y/O male K/C of polymyalgia rheumatica and essential tremor	Progressively worsening dyspnea, cough, bilateral crackles on auscultation On day 6: spontaneous macroscopic hematuria and bilateral epistaxis	16 days	ITP	Ceftriaxone, hydrocortisone, prednisolone, IVIG	Recovered (Plt started to increase the day following IVIG and normalized within 1 week)
Pedroso et al. [43]	1. 67 Y/O female K/C of HTN and ischemic stroke 2. 41 Y/O female K/C of T1DM and CKD	1. She was admitted due to traumatic subcapital right femur fracture and planned for surgery. In hospital course: cough, skin blood suffusions on puncture sites 2. Fever, myalgia, odynophagia, bilateral lumbar pain, dysuria and vomiting, minor self-limited hemorrhagic complications on the puncture sites	1. 16 days 2. 13 days	ITP	1. Plt did not respond to sole use of Plt transfusion; then, with steroid, Plt reached normal levels 2. No specific treatment for ITP	1. Recovered (Plt reached normal levels within 5 days; patient discharged on day 48) 2. Recovered (maintained hospitalized for surveillance and spontaneous Plt recovery)
Nesr et al. [44]	34 Y/O pregnant female in second trimester with a past history of ITP	Fever, dry cough, petechiae, gum bleeding	Less than 1 day	ITP	IVIG, prednisolone	Recovered (Plt rapidly raised on day 2 and the patient was discharged that day)
Metallidis et al. [45]	33 Y/O female K/C of T1DM	Low-grade fever, sore throat, mild myalgias, O2 sat: 98%	7 days	ITP	IVIG, dexamethasone	Recovered (Plt rapidly raised following the treatment and patient discharged about 9 days later)
Tsao et al. [46]	10 Y/O female	History of fatigue, non-productive cough and fever in 3 weeks ago, wet purpura in mouth, petechiae on her lower extremities, chest and neck, ecchymosis of popliteal regions and shins	About 20 days	ITP	IVIG, diphenhydramine, acetaminophen	Recovered (patient discharged at day 2 and had telehealth visits; rash and oral lesions improved within 48 h and Plt normalized in 2 weeks)
Tang et al. [47]	Pregnant female at the 41th weeks of pregnancy	Labor contractions, sore throat, O2 sat: 98%, no signs of easily bruising or bleeding	Not mentioned	ITP	IVIG, Plt transfusion	Recovered (Plt responded rapidly within 1 d)
de la Cruz-Benito et al. [14]	1. 94 Y/O patient K/C of HTN, chronic obstructive pulmonary disease and chronic ITP 2. 55 Y/O patient K/C of hyperlipidemia 3. 41 Y/O patient	1. Fever, persistent cough 2. Fever, dyspnea, persistent cough, myalgia/ arthralgia 3. Fever, dyspnea, persistent cough, myalgia/arthralgia, dysgeusia	Not mentioned	1.ITP relapse 2.New ITP 3. New ITP	1. HCQ 2. HCQ, IVIG 3. Steroid	Recovered (All cases had a good response after initial treatment, faster than is typically observed in other newly diagnosed cases. All the patients exhibited a Plt <7 days)
Murt et al. [48]	41 Y/O male	Cough, rhinorrhea, petechial and purpuric rash, nasal bleeding	15 days	ITP	Favipiravir, high-dose dexamethasone, IVIG	Recovered
Levraut et al. [49]	63 Y/O female K/C of autoimmune hypothyroidism and stroke	History of fever, dry cough and headaches in prior weeks, lower limb purpura, bruises of both arms and legs, bilateral crackles at lung bases	26 days	ITP	IVIG	Recovered (Plt started to increase the day following IVIG; patient was discharged on day 7)
Lobos et al. [50]	22 Y/O male	Petechia on extremities, gingival bleeding and buccal hematoma after a dental procedure	No symptoms of infection	ITP	IVIG, Eltrombopag	Recovered (patient discharged on day 6)
Kewan et al. [51]	89 Y/O male K/C of CHF, HTN, T2DM, CKD and AF (on warfarin)	Dyspnea, dry cough, diarrhea, crackles at lung base auscultation	16 days	ITP	HCQ, tazocin, azithromycin, IVIG, dexamethasone, Plt transfusion	Deceased (Plt responded to 2 days treatment course; patient deceased due to his poor condition)
Hayden et al. [52]	51 Y/O female K/C of long-standing SLE (18 years) and APLS, left below-knee amputation complicated by a perioperative cerebrovascular accident	Fever, 1 week hemoptysis, normal O2 sat	Not mentioned	ITP	The patient failed to respond to initial treatment with IVIG, high-dose steroid and Plt transfusion but responded to eltrombopag	Recovered (on day 8, the patient received first dose of eltrombopag and Plt normalized in 4 days; patient discharged on day 13)
Molinaro et al. [53]	19 Y/O female	Afebrile, fatigue, ageusia, normal O2 sat, diffuse purpuric lesions mostly on lower extremities	14 days	ITP	HCQ, antiretroviral agents, methylprednisolone, IVIG,	Recovered (Plt response initiated at day 3 and patient was discharged at day 5)
Mahévas et al. [15]	1. 58 Y/O female 2. 66 Y/O male 3. 62 Y/O female 4. 62 Y/O male 5. 74 Y/O male 6. 63 Y/O male 7. 65 Y/O male 8. 66 Y/O female 9. 79 Y/O female 10. 59 Y/O female 11. 61 Y/O female 12. 69 Y/O female 13. 53 Y/O male 14. 72 Y/O male	1. Fever, cough, purpura, epistaxis, oral hemorrhagic bullae 2. Fever, cough, anosmia, epistaxis 3. Fever, cough 4. Dyspnea 5. Fever, cough, purpura, mucosal bleeding, gastrointestinal bleeding 6. Fever, dyspnea, cough 7. Fever 8. Fever, dyspnea, cough, purpura, epistaxis, intracranial bleeding 9. Fever, dyspnea, cough, purpura 10. Fever, cough, purpura, mucosal bleeding 11. Fever, cough, anosmia, dysgeusia, purpura 12. Fever, dyspnea, cough, purpura, epistaxis, subcutaneous hematoma, gross hematuria 13. Fever, dyspnea, cough, purpura 14. Fever, dyspnea, cough, diarrhea	1. 10 days 2. 13 days 3. 5 days 4. 2 days 5. 12 days 6. 23 days 7. 22 days 8. 8 days 9. 16 days 10. 30 days 11. 25 days 12. 14 days 13. 27 days 14. 15 days	1. ITP 2. ITP 3. ITP 4. ITP+CLL 5. ITP 6. ITP 7. ITP 8. ITP 9. ITP 10. ITP 11. ITP 12. ITP 13. ITP 14. ITP	1. IVIG, eltrombopag 2. IVIG, eltrombopag 3. Prednisolone 4. Prednisolone 5. Prednisolone 6. Prednisolone 7. Dexamethasone 8. Methylprednisolone, IVIG, eltrombopag 9. IVIG 10. IVIG 11. IVIG 12. IVIG, romiplostim 13. IVIG, Prednisolone 14. IVIG	Recovered (significant response in all patient except for patients 3, 7 and 13 that had relapse on day 58, 30 and 35, responsively)
Pascolini et al. [54]	1. 69 Y/O female K/C of recently diagnosed cerebral lymphoma 2. 88 Y/O male K/C of CHF and recent hip replacement 3. 31 Y/O male	1. Admitted for pulmonary embolism while receiving chemotherapy 2. Flare of CHF 3. Fever and dyspnea	1. 7 days 2. Not mentioned 3. Not mentioned	ITP	1. Ceftriaxone, LMWH, dexamethasone 2. Methylprednisolone 3. HCQ, ceftriaxone, Prednisolone, LMWH	Recovered (All cases recovered but there is not much detail about recovery course)
Soares et al. [55]	2 Y/O female	Fever in prior weeks, bruises and petechiae throughout her body	More than 25 days	ITP	IVIG	Recovered (Plt normalized within 5 days after IVIG administration but relapsed on day 40 post-IVIG)
Clerici et al. [56]	64 Y/O male K/C of HTN and DM	Fever, epistaxis, mucocutaneous petechiae, wet purpura, left axillary lymphadenopathy	3 days	ITP+ Hodgkin’s lymphoma	Plt was unresponsive to steroids and IVIG but romiplostim administration increased Plt, Plt pool transfusions and bilateral tranexamic acid-soaked nasal tampons for epistaxis	Recovered (Plt responded to treatment with romiplostim within 1 week)
Kondo et al. [57]	58 Y/O female K/C of long-standing SLE (nearly 20 years) on prednisolone	2 days history of chest discomfort, O2 sat: 95% On day 6: gingival bleeding	2 days	ITP flare	Ciclesonide inhalation, IVIG	Recovered (Plt normalized after 5 days of IVIG)
Hu et al. [58]	72 Y/O female K/C of chronic ITP for 2 years (currently on prednisolone and cyclosporine)	Fever, productive cough	9 days	ITP flare	Arbidol, interferon α, darunavir/cobicistat, Plt failed to respond to IVIG but responded to methylprednisolone, Plt transfusion	Recovered (Plt normalized after 5 days of methylprednisolone administration)
Albiol et al. [59]	57 Y/O female K/C of HTN and breast cancer in complete remission	Fever, dry cough, anosmia, dysgeusia	6 days	TTP	HCQ, lopinavir/ritonavir, azithromycin, Plt did not respond to IVIG and methylprednisolone but did to plasma exchange	Recovered (Plt significantly raised within 24 h of plasma infusion)
Hindilerden et al. [10]	74 Y/O female K/C of HTN	Dry cough, progressive fatigue, pale, slightly subicteric, apathic confusion, fine bibasilar crackles	5 days	TTP	HCQ, favipiravir, azithromycin, plasma exchange, folic acid, aspirin methylprednisolone	Recovered (Plt raised significantly within 3 days of plasma exchange)
Capecchi et al. [60]	55 Y/O female K/C of TTP (caused by bacterial pneumonia thirty yrs. ago, successfully treated at the time with corticosteroids and plasma exchange)	Mild influenza-like symptoms, dyspnea, malaise, fatigue, chest discomfort, agitation and unconsciousness	3 days	TTP relapse	HCQ, ceftriaxone, azithromycin, caplacizumab, methylprednisolone, plasma exchange, aspirin	Recovered (Plt raised 6 h after the first injection of caplacizumab and normalized after 12 days of treatment; patient was discharged on 31)
Sung et al. [61]	49 Y/O obese female	Fever, progressive shortness of breath, cough, myalgia, rhinorrhea, loss of appetite, tachycardia, tachypnea, O2 sat: 87% On day 6: extremities swelling and pain	11 days	APLS	HCQ, ceftriaxone, azithromycin, LMWH	Recovered (after 3 days of anticoagulation and HCQ therapy, she was noted to have significant improvement in respiratory status and swelling of extremities)
Zhang et al. [62]	1. 69 Y/O male K/C of HTN, DM and stroke 2. 65 Y/O female K/C of HTN, DM and coronary artery disease and no history of thrombosis 3. 70 Y/O male K/C of HTN, emphysema, stroke and nasopharyngeal carcinoma	1. Fever, dyspnea, cough, diarrhea, headache, evidence of ischemia in the lower limbs bilaterally as well as in digits two and three of the left hand 2. Fever, dyspnea cough 3. Fever, dyspnea, headache fatigue	1. 18 days 2. 33 days 3. 10 days	APLS	1. Oseltamivir, IVIG 2. Antibiotics 3. Antibiotics, ribavirin, rosuvastatin	Not mentioned
Escher et al. [63]	72 Y/O male	6 days history of fever and respiratory symptoms On day 6: rapid deterioration of clinical condition with development of acute respiratory distress syndrome, acute renal insufficiency and altered mental status	More than 12 days	APLS	Prophylactic dalteparin which was replaced with therapeutic dose of LMWH on day 21	Recovered (not much detain on the recovery course)
Hossri et al. [64]	1. 29 Y/O female K/C of hemoglobin S-C disease 2. 58 Y/O male K/C of dyslipidemia	1. Fever, non-productive cough, vomiting, abdominal pain, generalized myalgia, tachycardia, bibasilar crackles, lethargy, altered mental status, O2 sat: 99% 2. Fever, shortness of breath, non-productive cough, tachycardia, cold left lower extremity with mild pallor and cyanosis with absent dorsalis pedis and posterior tibialis pulses	1. 10 days 2. 15 days	APLS	1. HCQ, tocilizumab, therapeutic heparin 2. HCQ, azithromycin, anakinra, LMWH	Not mentioned
Maria et al. [65]	48 Y/O male K/C of primary APLS (revealed by venous thromboembolic event) treated since 2013 with vitamin K antagonists	Fever, cough, myalgia, mild hypoxemia (pO2: 75 mm Hg), O2 sat: 96% On day 7: sudden abdominal pain (bilateral adrenal glands hemorrhage) On day 12: painful acral ischemic lesions concerning left toes (dorsalis pedis artery occlusion)	12 days	APLS flare	HCQ and azithromycin, VKA switched for LMWH on day 7. On day 12, LMWH was replaced by IV continuous unfractionated heparin (anti-Xa)	Recovered (there was no other clinical or radiological thrombotic event occurred after administration of unfractionated heparin and patient was discharged on day 22)
Cardoso et al. [66]	18 Y/O female K/C of autism spectrum disorder and panic disorder	History of productive fever, dyspnea, cough and malaise in prior weeks, tachypnea, tachycardia, hypotension, hemodynamic collapse and respiratory failure which progressed to cardiac arrest and had a pericardial tamponade drained, severe ventricular dysfunction (EF: 20–25%) and worsening renal function with proteinuria and hematuria requiring hemodialysis, multiple DVT	More than 14 days	SLE and possible APLS	HCQ, ceftazidime, vancomycin, azithromycin, tocilizumab, steroids, plasma exchange, anticoagulation	Deceased (plasmapheresis was discontinued due to a concern of possible removal of antibodies needed for the adaptive response to infection; patient deceased on day 17)
Frankel et al. [67]	66 Y/O female with past history of multiple abortions	Fever, dyspnea, vomiting and nausea, abdominal pain, history of one episode syncope, decreased blood pressure diffuse abdominal tenderness, O2 sat: 94%	5 days	APLS	Steroid	Recovered (patient was discharged on day 11)

AF, atrial fibrillation; AIHA, autoimmune hemolytic anemia; APLS, antiphospholipid syndrome; CHF, congestive heart failure; CKD, chronic kidney disease; HCQ, hydroxychloroquine; HTN, hypertension; ITP, idiopathic thrombocytopenic purpura; IV, intravenous; IVIG, intravenous immunoglobulin; K/C, known case; LMWH, low molecular weight heparin; SLE, systemic lupus erythematosus; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; TTP, thrombotic thrombocytopenic purpura; Y/O, year-old.

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