Rapidly Fatal COVID-19-associated Acute Necrotizing Encephalopathy in a Previously Healthy 26-year-old Man

Robert A. Raschke MD and Cristian Jivcu MD

HonorHealth Scottsdale Osborn Medical Center

Scottsdale, AZ USA

Case Presentation

A 26-year-old man presented to our Emergency Department at 0200 on the day of admission with chief complaints of subjective fever, leg myalgias, and progressive dyspnea of one week duration. An oropharyngeal swab PCR had revealed SARS-CoV-2 RNA three days previously. He had not received a SARS CoV-2 vaccination, but had made an appointment to receive it just a few days prior to the onset of his symptoms.

The patient had no significant past medical history, was taking no medications except for ibuprofen and acetaminophen over the past week, and did not take recreational drugs. He specifically denied headache and had no prior history of seizure.

On admission, his HR was 150 bpm (sinus), RR 22, BP 105/46 mmHg, temp 40.2° C. and SpO₂ 92% on room air. He was ill-appearing, but alert and oriented, his neck was supple and lung auscultation revealed bilateral rhonchi, but physical examination was otherwise unremarkable.

A CBC showed WBC 17.3 10³/uL, hemoglobin 13.9 g/dl, and platelet count 168 K/uL. A complete metabolic profile was normal except for the following: Na 135 mmol/L, creatinine 1.7 mg/dL, AST 95 and ALT 134 IU/L. D-dimer was 1.08 ug/ml (normal range 0.00-0.50 ug/ml), and ferritin 783 ng/ml. A urine drug screen was negative. Chest radiography showed subtle bilateral pulmonary infiltrates. CT angiography of the chest was negative for pulmonary embolism but showed bilateral patchy infiltrates consistent with COVID19 pneumonia. One liter NS bolus and dexamethasone 10mg were given intravenously, acetaminophen administered orally, and the patient was admitted to telemetry.

Shortly thereafter, the patient experienced a brief generalized seizure associated with urinary incontinence. He was stuporous post-ictally, exhibiting only arm flexion to painful stimuli. A stroke alert was called and radiographic studies emergently obtained. CT of the brain was normal and CT angiography of the head and neck showed no large vessel occlusion or flow-limiting stenosis, and a CT perfusion study (Figure 1) showed patchy Tmax prolongation in the right cerebellum and bilateral parietal occipital lobes “which may reflect artifact or relative ischemia” with no matching core infarct.

Figure 1. CT perfusion study showing mild bilateral posterior distribution ischemia (Tmax > 6 secs) without matching core infarct (CBF<30%), interpreted by a neuroradiologist as possible artifact.

The patient was transferred to the ICU at 10:00, and experienced a 40-second generalized tonic-clonic seizure shortly thereafter. Lorazepam 2mg was administered intravenously. The HR was 104, RR 21, BP 105/61, temp 36.5 C. and SpO₂ 96% on 2L /min nasal canula oxygen. On neurological examination, the Glasgow Coma Scale was 3, right pupil was 3mm, left pupil 2mm - both reactive, the gaze was disconjugate and directed downward, there was no blink to visual threat, and glabellar ridge pressure did not elicit grimace, but minimal arm flexion. The gag reflex was positive. Peripheral reflexes were 2+ with down-going toes bilaterally. Levetiracetam 1000mg bolus was administered intravenously. Glucose was 147 mg/dL. An EEG obtained at 12:00 showed diffuse bilateral slowing without seizure activity. A presumptive diagnosis of post-ictal encephalopathy was made. The patient seemed to be protecting his airway and nasal canula oxygen was continued.

The patient’s condition was not noted to significantly change over the next 12 hours. There were no episodes of hypoxia, hypotension or hypoglycemia. Around 0100 on the second day of hospitalization, the patient exhibited extensor-posturing and appeared to be choking on his oral secretions. HR rose to 135, BP 155/99, RR 12 and temp 37.8 C. His SpO₂ fell into the mid 80% range. He no longer had a gag or cough reflex and he was emergently intubated without complication. MRI (Figure 2) and MRV of the brain were emergently obtained. 

Figure 2. A: T2-weighted image demonstrating bilateral thalamic and L occipital white matter hypoattenuation. B: DWI and GRE images showing bilateral thalamic infarctions with hemorrhage. C: Representative DWI images of cerebrum and cerebellum and pons showing widespread diffusion restriction.

The MRI showed extensive diffusion restriction involving bilateral thalami, cerebellar hemispheres, pons, and cerebral hemispheres with scattered hemorrhage most obvious/confluent in the bilateral thalami.

Normal flow voids were present in intracranial arteries and venous structures. Partial effacement of the lateral and third ventricles was noted, with early uncal herniation. The MRV showed no evidence of dural venous sinus thrombosis.

At 05:00 of the second hospital day, it was noted that the patient’s pupils were dilated and unreactive and his respiratory rate was 16 – equal to the respiratory rate set on the ventilator. BP fell to 85/45 and norepinephrine infusion was started to maintain MAP >65 mmHg. STAT CT brain (Figure 3) showed hemorrhagic infarcts of the bilateral thalami with surrounding edema, interval development of low attenuation of the bilateral cerebrum and cerebellum, and mass effect with total effacement of fourth ventricle, basal cisterns and cerebral sulci consistent with severe cerebral edema.

Figure 3. STAT CT brain from 05:30 on the second hospital day showing bilateral thalamic infarctions and diffuse cerebral edema with effacement of the sulci and loss of grey/white differentiation.

Two neurologists confirmed the clinical diagnosis of brain death, including an apnea test. A venous ammonia level ordered that morning was not drawn. An autopsy was requested by the physicians, but not able to be obtained.

Discussion

Acute necrotizing encephalopathy (ANE) is a rarely-reported clinical-radiographic syndrome lacking pathopneumonic laboratory test or histological findings (1-3). It is characterized by an acute febrile viral prodrome, most commonly due to influenza or HHV-6, followed by rapidly progressive altered mental status and seizures. The most specific finding of ANE is necrosis of the bilateral thalami, appearing on MRI as hypoattenuated lesions on T2 and FLAIR images with diffusion restriction on DWI, and often with hemorrhage demonstrated on GRE images (as shown in figure 2 above). Symmetric multifocal lesions are typically seen throughout various other locations in the brain including the cerebral periventricular white matter, cerebellum, brainstem and spinal cord. Mizuguchi (who first described ANE in 1995) proposed elevation of serum aminotransferase without hyperammonemia, and cerebrospinal albuminocytologic dissociation (elevated CSF protein without leukocytosis) as laboratory criteria supporting the diagnosis of ANE (1,2). These were only partially evaluated in our patient. The mortality of ANE is 30% and significant neurological sequelae are common in survivors (2).

The clinical, radiographic and laboratory findings in our case are all characteristic of ANE, but our work-up was abbreviated by the patient’s fulminant presentation. The differential diagnosis includes hyper-acute forms of acute disseminated encephalomyelitis (ADEM) or acute hemorrhagic leukoencephalitis that may also occur after a viral prodrome and may be associated with diffuse white matter lesions (4,5), although bilateral thalamic necrosis is not characteristic of either of these entities. Examination of cerebral spinal fluid (CSF) for pleocytosis, oligoclonal bands, and testing for the myelin oligodendrocyte glycoprotein IgG autoantibody and the aquaporin-4 IgG serum autoantibody would have been indicated to further evaluate for the initial presentation of a relapsing CNS demyelinating disease (5,6). CSF examination would also have been helpful in ruling out viral encephalitis affecting the thalami, such as that caused by West Nile Virus (WNV) (7). An acute metabolic encephalopathy with diffuse brain edema, such as that caused by severe hyperammonemia associated with late-onset ornithine transcarbamylase deficiency (8) was not ruled out. Arterial or venous thromboembolism associated with COVID-19 were effectively ruled out by CT angiogram, CT perfusion and MRI and MRV findings.    

We found five previous case reports of ANE as a complication of COVID-19, ranging 33-59 years of age (9-13). The onset of altered mental status occurred 3, 4, 7,10 and 21 days after onset of COVID-19 symptoms and rapidly progressed to coma. Two had generalized seizures, one myoclonus and another “rhythmic movements” of an upper extremity. All had bilateral hypoattenuation of the thalami on CT and MRI with variable involvement of temporal lobes, subinsular regions, cerebellum, brainstem and supratentorial grey and white matter. Two patients had EEGs that showed generalized slow waves. All underwent examination of CSF with negative PCR tests for various common encephalopathy viruses including herpes simplex virus 1&2 and WNV - four reported CSF protein and cell counts, three of which demonstrated albuminocytologic dissociation. Three patients received IVIG. Two patients died on days 5 and 8 after onset of neurological symptoms. Two recovered after prolonged ICU care and the outcome of the third patient was not reported. ANE may be less rare than these few case reports suggest. A retrospective study carried out at 11 hospitals in Europe describes radiographic findings of 64 COVID-19 patients with neurological symptoms (14). The most common finding was ischemic stroke, but 8 patients had MRI findings consistent with encephalitis and two had findings characteristic of ANE.

The pathogenesis of ANE is unknown. Ten cases of fatal ANE with brain biopsy are reported (1,15-19). These showed diffuse cerebral edema, and hemorrhagic necrosis invariably involving the thalami. An exudative small vessel vasculopathy with endothelial necrosis was found in 7/10 patients (This could perhaps explain the early CT perfusion findings interpreted as artifactual in our patient). Demyelination or inflammatory infiltration of the brain or leptomeninges was absent. There has been conjecture that these pathological findings might be due to disruption of the blood brain barrier caused by hypercytokinemia but there is scant supportive evidence (20). 

There is no proven treatment for ANE. Corticosteroids, IVIg and plasma exchange have been previously used (3,9-11,21). Clinical trials are unlikely given the rarity of the disorder.

It was unfortunate that this young man had not availed himself of SARS CoV-2 vaccination. We did not make a pre-mortem diagnosis of ANE between his first abnormal CT brain at 0100 and his death at 06:00. We would have performed an LP, measured serum ammonia and given a trial of corticosteroids and IVIg if we had had more time.

References

1. Mizuguchi M, Abe J, Mikkaichi K, Noma S, Yoshida K, Yamanaka T, Kamoshita S. Acute necrotising encephalopathy of childhood: a new syndrome presenting with multifocal, symmetric brain lesions. J Neurol Neurosurg Psychiatry. 1995 May;58(5):555-61. [CrossRef] [PubMed]
2. Mizuguchi M. Acute necrotizing encephalopathy of childhood: a novel form of acute encephalopathy prevalent in Japan and Taiwan. Brain Dev. 1997 Mar;19(2):81-92. [CrossRef] [PubMed]
3. Wu X, Wu W, Pan W, Wu L, Liu K, Zhang HL. Acute necrotizing encephalopathy: an underrecognized clinicoradiologic disorder. Mediators Inflamm. 2015;2015:792578. [CrossRef] [PubMed]
4. Marchioni E, Ravaglia S, Montomoli C, et al. Postinfectious neurologic syndromes: a prospective cohort study. Neurology. 2013 Mar 5;80(10):882-9. [CrossRef] [PubMed]
5. Manzano GS, McEntire CRS, Martinez-Lage M, Mateen FJ, Hutto SK. Acute Disseminated Encephalomyelitis and Acute Hemorrhagic Leukoencephalitis Following COVID-19: Systematic Review and Meta-synthesis. Neurol Neuroimmunol Neuroinflamm. 2021 Aug 27;8(6):e1080. [CrossRef] [PubMed]
6. López-Chiriboga AS, Majed M, et al. Association of MOG-IgG Serostatus With Relapse After Acute Disseminated Encephalomyelitis and Proposed Diagnostic Criteria for MOG-IgG-Associated Disorders. JAMA Neurol. 2018 Nov 1;75(11):1355-1363. [CrossRef] [PubMed]
7. Guth JC, Futterer SA, Hijaz TA, Liotta EM, Rosenberg NF, Naidech AM, Maas MB. Pearls & oy-sters: bilateral thalamic involvement in West Nile virus encephalitis. Neurology. 2014 Jul 8;83(2):e16-7. [CrossRef] [PubMed]
8. Cavicchi C, Donati M, Parini R, et al. Sudden unexpected fatal encephalopathy in adults with OTC gene mutations-Clues for early diagnosis and timely treatment. Orphanet J Rare Dis. 2014 Jul 16;9:105. [CrossRef] [PubMed]
9. Poyiadji N, Shahin G, Noujaim D, Stone M, et al.  COVID19-associated acute necrotizing encephalopathy: CT and MRI features.  Radiology. 2020;296:E119-E120. [CrossRef]
10. Virhammar J, Kumlien E, Fällmar D,et al. Acute necrotizing encephalopathy with SARS-CoV-2 RNA confirmed in cerebrospinal fluid. Neurology. 2020 Sep 8;95(10):445-449. [CrossRef] [PubMed]
11. Delamarre L, Galion C, Goudeau G, et al. COVID-19-associated acute necrotising encephalopathy successfully treated with steroids and polyvalent immunoglobulin with unusual IgG targeting the cerebral fibre network. J Neurol Neurosurg Psychiatry. 2020 Sep;91(9):1004-1006. [CrossRef] [PubMed]
12. Dixon L, Varley J, Gontsarova A, Mallon D, Tona F, Muir D, Luqmani A, Jenkins IH, Nicholas R, Jones B, Everitt A. COVID-19-related acute necrotizing encephalopathy with brain stem involvement in a patient with aplastic anemia. Neurol Neuroimmunol Neuroinflamm. 2020 May 26;7(5):e789. [CrossRef] [PubMed]
13. Elkady A, Rabinstein AA. Acute necrotizing encephalopathy and myocarditis in a young patient with COVID-19. Neurol Neuroimmunol Neuroinflamm Sep 2020, 7 (5) e801. [CrossRef]
14. Kremer S, Lersy F, Anheim M, et al. Neurologic and neuroimaging findings in patients with COVID-19: A retrospective multicenter study. Neurology. 2020 Sep 29;95(13):e1868-e1882. [CrossRef] [PubMed]
15. Kirton A, Busche K, Ross C, Wirrell E. Acute necrotizing encephalopathy in caucasian children: two cases and review of the literature. J Child Neurol. 2005 Jun;20(6):527-32. [CrossRef] [PubMed]
16. Mastroyianni SD, Gionnis D, Voudris K, Skardoutsou A, Mizuguchi M. Acute necrotizing encephalopathy of childhood in non-Asian patients: report of three cases and literature review. J Child Neurol. 2006 Oct;21(10):872-9. [CrossRef] [PubMed]
17. Nakano I, Otsuki N, Hasegawa A. Acute Stage Neuropathology of a Case of Infantile Acute Encephalopathy with Thalamic Involvement: Widespread Symmetrical Fresh Necrosis of the Brain. Neuropathology 1993;13: 315-25. [CrossRef]
18. Yagishita A, Nakano I, Ushioda T, Otsuki N, Hasegawa A. Acute encephalopathy with bilateral thalamotegmental involvement in infants and children: imaging and pathology findings. AJNR Am J Neuroradiol. 1995 Mar;16(3):439-47. [PubMed]
19. San Millan B, Teijeira S, Penin C, Garcia JL, Navarro C. Acute necrotizing encephalopathy of childhood: report of a Spanish case. Pediatr Neurol. 2007 Dec;37(6):438-41. [CrossRef] [PubMed]
20. Wang GF, Li W, Li K. Acute encephalopathy and encephalitis caused by influenza virus infection. Curr Opin Neurol. 2010 Jun;23(3):305-11. [CrossRef] [PubMed]
21. Okumura A, Mizuguchi M, Kidokoro H, et al. Outcome of acute necrotizing encephalopathy in relation to treatment with corticosteroids and gammaglobulin. Brain Dev. 2009 Mar;31(3):221-7. [CrossRef] [PubMed]

Cite as: Raschke RA, Jivcu C. Rapidly Fatal COVID-19-associated Acute Necrotizing Encephalopathy in a Previously Healthy 26-year-old Man. Southwest J Pulm Crit Care. 2021;23(5):138-43. doi: https://doi.org/10.13175/swjpcc039-21 PDF

Choosing Among Unproven Therapies for the Treatment of Life-Threatening COVID-19 Infection: A Clinician’s Opinion from the Bedside

Robert A. Raschke, MD

HonorHealth Scottsdale Osborn Medical Center

Scottsdale, AZ USA

We are clearly in unprecedented times. As clinicians watch patients die from COVID-19 infection in the ICU, many feel they cannot wait for clinical trials to prove that various proposed therapies are efficacious. Treatments for which any rationale suggest the possibility of benefit are being administered to patients and the literature abounds with reports of case series or poorly-designed observational trials in which small numbers of patients seem to have favorable outcomes when given these unproven therapies (1). In many cases, these reports are made globally available via social networking without the benefit of peer-review or are being published despite severe methodological flaws that would not have been acceptable prior to the COVID-19 outbreak. 

Standard therapy for COVID-19 has recently been published by the Surviving Sepsis Campaign, which have taken a conservative, evidence-based approach (2). But many clinicians are not able to maintain such equipoise in the face of catastrophe. Therefore, I propose an approach to consideration of bedside implementation of unproven therapies for life-threatening COVID-19 for comment and criticism. None of the therapies discussed below have even marginally-acceptable empirical evidence of clinical benefit in patients with COVID-19, so let us put critical appraisal of the literature aside for the moment, and accept that we cannot evaluate these therapies using the normal rules of evidence-based practice (3), application of which would exclude all from further consideration were this any other disease than COVID-19.

I will focus on four unproven therapies that are currently being given to patients with COVID-19 infection: hydroxychloroquine (4), tissue plasminogen activator (tPA) and heparin for presumed pulmonary microthrombosis (5), immunosuppressive treatment of “cytokine storm” (6), and transfusion of convalescent serum (7).

I based my opinions on these four unproven therapies on the following principles:

1. COVID-19 is a viral pneumonia. Although it may prove to have some distinctive features, it is likely to be similar to other viral pneumonias (such as SARS CoV-1, MERS, and H1N1 influenza) in terms of its clinical manifestations and response to therapy. We are more likely to gain helpful insights by looking at previous clinical data related to viral pneumonia than to data regarding various noninfectious entities such as high-altitude pulmonary edema or pulmonary venous occlusive disease, as some authors have suggested. COVID-19 viral pneumonia is unlikely, a priori, to respond to therapies that have never shown clinical benefit in the treatment of other viruses, particularly viral pneumonias.
2. Demonstration of in-vitro activity rarely translates into clinical efficacy (8,9). In-vitro activity should be a basis for clinical trials, not bedside implementation.
3. If unproven therapies are to be given, their safety must be an important consideration. First do no harm.
4. We should be willing to apply any treatment recommendation we make for patients to ourselves or beloved family members.

Based on these principles, I propose the following:

Hydroxychloroquine. The non-specific anti-viral properties of chloroquine and hydroxychloroquine were demonstrated in cell cultures 40 years ago. Although active in vitro against Dengue, HIV, Ebola, Influenza and other viruses, this has never convincingly translated into clinical effectiveness (9). A large cohort study focusing on prevention of influenza pneumonia included over 4000 patients receiving HCQ, and showed that they had an increased risk of hospitalization for pneumonia compared to controls (10). Given this long track record, it seems unlikely that HCQ will suddenly be found to have clinical anti-viral benefit in 2020. When it is nevertheless given, care should be exercised to monitor QTc, especially if used in conjunction with other QTc-prolonging drugs like azithromycin and/or in patients with cardiomyopathy.

tPA and heparin. A high incidence of venous thromboembolism has been observed in some cohorts of COVID-19 patients, as has previously been described in patients with H1N1 pneumonia (11).  Standard thromboprophylaxis should be employed and venous thromboembolism should be diagnosed and treated in patients with COVID-19 infection. However, some clinicians are administering tPA and therapeutic-dose heparin to patients with COVID-19 and elevated D-dimer in the absence of documented DVT or PE, based on the theory that these patients have microvascular thrombosis requiring treatment. Several large multicenter RCTs examined the use of human activated protein C (Xigris®) to prevent/treat microvascular thrombosis in patients with severe sepsis and convincingly demonstrated no clinical benefit (12). There is no other infectious disease for which the use of tPA or treatment-dose heparin has been proven to be clinically beneficial in the absence of standard indications related to documented venous thromboembolism. Lytic/antithrombotic therapy has a relatively high potential for causing life-threatening hemorrhage. In my opinion, it should not be employed without support from well-designed clinical trials. 

Cytokine Storm or HLH. The terms cytokine storm and hemophagocytic lymphohistiocytosis (HLH) have been used to describe similar (perhaps identical) maladaptive immune responses to viral infections. HLH has been well-described in H1N1 pneumonia, SARS-CoV-1 and MERS. There is a rich history of (mostly) observational clinical research supporting the use of immunosuppressive therapies including steroids, anakinra and tocilizumab to treat HLH secondary to viral infection (13). Although immunosuppression can be associated with life-threatening secondary opportunistic infections, treating secondary HLH in selected patients is an approach with a long track record and could be considered standard therapy in Covid19 patients fulfilling HLH diagnostic criteria.

Convalescent Serum. The use of convalescent serum is supported by low-quality observational data going back over 100 years. Although never proven effective in well-designed clinical trials, prior reports in patients with Spanish influenza, SARS-CoV-1 and H1N1 all suggest potentially significant reductions in mortality with acceptable safety (14-16). This therapy is more difficult to operationalize, requiring (expedited) FDA approval, collection, processing and testing of neutralizing antibody titers by a licensed blood bank (17), however based on the principles outlined above, its benefit/harm ratio seems to support its use as an investigational therapy in patients with life-threatening COVID-19.

References

1. Booth CM, Tannock IF. Randomised controlled trials and population-based observational research: partners in the evolution of medical evidence. Br J Cancer 2014;110:551-5. [CrossRef] [PubMed]
2. Alhazzani W, Møller MH, Arabi YM, et al. Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19). Crit Care Med. 2020 Mar 27. [Epub ahead of print]. [CrossRef] [PubMed]
3. Guyatt GH, Sackett DL, Cook DJ. Users' guides to the medical literature. II. How to use an article about therapy or prevention. A. Are the results of the study valid? Evidence-Based Medicine Working Group. JAMA. 1993 Dec 1;270(21):2598-601. [CrossRef] [PubMed]
4. Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial [published online ahead of print, 2020 Mar 20]. Int J Antimicrob Agents. 2020;105949. [CrossRef] [PubMed]
5. Wang J., Hajizadeh N, Moore EE, et al. Tissue plasminogen activator (tpa) treatment for COVID‐19 associated acute respiratory distress syndrome (ARDS): a case series. J Thromb Haemost. 2020 (in press). [CrossRef] [PubMed]
6. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-4.[CrossRef] [PubMed]
7. Duan K, Liu B, Cesheng L, Zhang H, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci U S A. 2020 Apr 6. pii: 202004168. [CrossRef] [PubMed]
8. Seyhan, A.A. Lost in translation: the valley of death across preclinical and clinical divide - identification of problems and overcoming obstacles. Transl Med Commun. 2019;4:18. [CrossRef]
9. Dyall J, Gross R, Kindrachuk J, et al. Middle east respiratory syndrome and severe acute respiratory syndrome: current therapeutic options and potential targets for novel therapies. Drugs. 2017;77:1935-66. [CrossRef] [PubMed]
10. Vanasse A, Courteau J, Chiu Y, Cantin A, Leduc R. Hydroxychloroquine: an observational cohort study in primary and secondary prevention of pneumonia in an at-risk population. MedRxIv .April 10, 2020. [CrossRef]
11. Bunce PE, High SM, Nadjafi M, Stanley K, Liles WC, Christian MD. Pandemic H1N1 influenza infection and vascular thrombosis.Clin Infect Dis. 2011 Jan 15;52(2):e14-7.
12. Ranieri VM, Thompson BT, Barie PS, et al. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med. 2012 May 31;366(22):2055-64. [CrossRef] [PubMed]
13. Yildiz H, Van Den Neste E, Defour JP, Danse E, Yombi JC. Adult haemophagocytic lymphohistiocytosis: a review. QJM. 2020 Jan 14. [Epub ahead of print] [CrossRef] [PubMed]
14. Luke TC, Kilbane EM, Jackson JL, et al. Meta-analysis: convalescent blood products for spanish influenza pneumonia: a future H5N1 treatment?. Ann Intern Med. 2006;145:599-609. [CrossRef] [PubMed]
15. Hung IF, To KK, Lee CK, et al. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis. 2011 Feb 15;52(4):447-56. [CrossRef] [PubMed]
16. Yeh KM, Chiueh TS, Siu LK, et al. Experience of using convalescent plasma for severe acute respiratory syndrome among healthcare workers in a Taiwan hospital. J Antimicrob Chemother. 2005 Nov;56(5):919-22. [CrossRef] [PubMed]
17. US Food & Drug Administration. Recommendations for Investigational COVID-19 Convalescent Plasma. April 8, 2020. Available at:https://www.fda.gov/vaccines-blood-biologics/investigational-new-drug-ind-or-device-exemption-ide-process-cber/recommendations-investigational-covid-19-convalescent-plasma (accessed 4/10/20).

Cite as: Raschke RA. Choosing among unproven therapies for the treatment of life-threatening covid-19 infection: a clinician’s opinion from the beside. Southwest J Pulm Crit Care. 2020;20(4):131-4. doi: https://doi.org/10.13175/swjpcc026-20 PDF 

April 2020 Critical Care Case of the Month: Another Emerging Cause for Infiltrative Lung Abnormalities

Henry W. Luedy, MD¹

Sandra L. Till, DO²

Robert A. Raschke, MD¹

¹HonorHealth Scottsdale Osborn Medical Center

²Banner University Medical Center-Phoenix

Phoenix, AZ USA

Editor’s Note: the following case presentation represents a compilation of several patients.

History of Present Illness

The patient is a 27-year-old man who presented to the Emergency Department in late February 2020 with fever, cough, and green sputum production. He was recently in Hawaii where he meant his Asian girlfriend and was “partying hard”. He was intoxicated and had recent nausea and vomiting.

PMH, SH and FH

No significant PMH or FH. He does admit to smoking, marijuana use, THC use, and vaping. 

Physical Examination

• Vital Signs: BP 111/54 (BP Location: Right arm)  | Pulse 74  | Temp 98.7 °F (37.1 °C) (Oral)  | Resp 18  | Ht 5' 11" (1.803 m)  | Wt 72.6 kg (160 lb)  | SpO2 99%  | BMI 22.32 kg/m²
• General:  Awake, alert, interactive, no acute distress
• HEENT:  Anicteric, moist mucosa, trachea midline
• CV:  RRR
• Lungs: bilateral lower lobe rhonchi, no wheezing, symmetric expansion
• Abdomen: Soft, non-tender, non-distended, positive bowel sounds
• Extremities: no Lower extremity edema, no clubbing, no cyanosis
• Neuro:  No focal deficits, moves all extremities.
• Psych:  Appropriate

Which of the following are appropriate at this time? (Click on the correct answer to be directed to the second of six pages.)

1. CBC
2. Chest X-ray
3. Electrolytes
4. 1 and 3
5. All of the above

Cite as: Luedy HW, Till SL, Raschke RA. April 2020 critical care case of the month: another emerging cause for infiltrative lung abnormalities. Southwest J Pulm Crit Care. 2020;20(4):119-23. doi: https://doi.org/10.13175/swjpcc018-20 PDF