Successful Outcomes of Severe COVID-19 in Patient with Chronic Lymphocytic Leukemia: Diagnostic Challenges in Immunocompromised Hosts
E. Malek1*, Cristina Gutierrez2*,
Victor E. Mulanovich1, Joshua Botdorf2,
Roy F. Chemaly1, Shivan Shah1,
Brandi M. McCall2, Judd T. Melancon2,
Kelly K. McConn1, Jovan Borjan3,
Issam I. Raad1, Jan A. Burger4,
Guillermo Garcia-Manero4 and Javier A. Adachi1..
of Infectious Diseases, Infection Control and Employee Health. The
University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd.,
Houston, TX 77030, USA.
2 Department of Critical Care Department; The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
3 Division of Pharmacy; The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
4 Department of Leukemia; The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
* Alexandre E. Malek and Cristina Gutierrez are first Co-authors.
Received: May 13, 2020
Accepted: June 15, 2020
Mediterr J Hematol Infect Dis 2020, 12(1): e2020044 DOI 10.4084/MJHID.2020.044
| This is an Open Access article distributed
under the terms of the Creative Commons Attribution License
(https://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
emergence and spread of 2019 novel coronavirus have led to an
unprecedented public health crisis around the globe, threatening the
lives of millions of people. We report a severe case of COVID-19 in a
patient with chronic lymphocytic leukemia and describe primarily the
clinical presentation and the challenges encountered in the COVID-19
diagnosis, treatment, and specimens sampling pitfalls. This case
highlights the importance of a comprehensive diagnostic approach of
pneumonia in immunocompromised hosts, including timely and safe
bronchoscopy, because of the broad differential diagnosis, more
challenging with the current outbreak of COVID-19.
While currently, around 15 million people are living with cancer, little is known about the burden of COVID-19 in cancer patients who are at increased risk of worse outcomes. Here we present a case of severe COVID-19 in a patient with chronic lymphocytic leukemia (CLL) who initially evaded a timely diagnosis, but she successfully recovered after 17 days of intubation.
Ten days after symptoms onset, she presented to the Emergency Department (ED) with two days of dry cough, shortness of breath, myalgias, and persistent fevers of 102 °F (38.9 °C). The signs and symptoms are outlined in Figure 1. She denied recent international or domestic travel or contact with known or suspected COVID-19 cases. In the ED, she was hypoxic with SpO2 85% on 6 L/min nasal cannula. She was placed on a non-rebreather mask (15 L/min of oxygen) and was later electively intubated and placed on mechanical ventilation with a lung-protective strategy. Empiric therapy with cefepime 2 g IV Q 12 hours, linezolid 600 mg IV Q 12h and doxycycline were initiated. A posteroanterior chest radiograph showed bilateral diffuse lung opacities (Figure 2, panel a).
Her laboratory studies were notable for: white blood cell count 11,700 /µl with 61% neutrophils and 35% lymphocytes, a relative lymphocytopenia in the setting of CLL. Troponin level <6 ng/L and total immunoglobulin G, 839 mg/dL. The remaining laboratory results are summarized in Table 1. A nasopharyngeal (NP) swab specimen was negative for common respiratory viruses. This specimen was collected in accordance with the Centers for Disease Control and Prevention and was negative for reverse transcriptase (rRT)-polymerase-chain-reaction (PCR) for SARS-CoV-2.
|Table 1. Clinical Laboratory Results.|
A chest computed tomography (CT) scan was performed on hospital day (HD) 2 and showed bilobar multi-segmental ground-glass opacities (GGO) located both centrally and peripherally (Figure 2, panel b). Despite negative testing, COVID-19 pneumonia was highly suspected. A second NP swab specimen for SARS-CoV-2 was performed and reported negative. Blood cultures, serum Aspergillus antigen, βeta-(1,3)-d-glucan, and urine legionella antigen were all negative.
In view of the second negative COVID testing, and the patient’s risk factors for opportunistic infections, a bronchoscopy with bronchoalveolar lavage (BAL) was performed. Precautions to avoid generating aerosolized particles were taken, such as the use of personal protective aerosolized equipment (PAPR) and paralyzing the patient during the procedure. The BAL specimen was negative for aspergillus antigen, pneumocystis jirovecii PCR, cytomegalovirus PCR, bacterial and fungal cultures. However, the BAL rRT-PCR for SARS-CoV-2 was positive on HD 4. The treatment was transitioned to hydroxychloroquine 400 mg twice daily for two doses, then 200 mg twice daily combined with azithromycin 500 mg first dose, then 250 mg once daily for a total of 5 days. Additionally, two doses of tocilizumab of 8 mg/kg every 12 hours were administered on HD 4 with one infusion of immunoglobulins (30 g). The patient developed acute respiratory distress syndrome (ARDS), and she was dependent on mechanical ventilation thereafter. On HD12, a short course of high dose intravenous methylprednisolone 1 mg/kg per day was administered and which resulted in a gradual improvement of the patient’s respiratory status. Five days after the initiation of corticosteroids (HD17), the patient was successfully extubated. Before discharge, a repeat SARS-CoV-2 PCR from NP specimen remained negative. She responded well to skilled occupational therapy exercises and, on HD 28, she was discharged home on room air, with stable conditions, and without sequelae. After one month of discharge, serologic testing for COVID-19 (Viracor Eurofins) showed positive IgG, 56.6 Units (normal range, ≤ 9.0 Units).
Our patient initially reported GI symptoms in the absence of respiratory symptoms, which did not develop until a week into the illness. The GI manifestations of COVID-19 have been described in 2 to 10% in cases series and an observational study (N=1099) reported the presence of nausea or vomiting (5.0%) and diarrhea (3.8%) in infected patients. However, other studies showed that up to 11% of patients had on admission at least one GI symptom, and around 50% of patients developed GI symptoms during the hospitalization.[8,9] Early nonspecific symptoms of COVID-19 can lead to diagnostic difficulty in distinguishing between other common infectious diseases.
The SARS-CoV-2 has been detected in nasopharyngeal, oropharyngeal, sputum, and BAL specimens in COVID-19. BAL samples are the most accurate but involve dedicated personnel and invasive procedures for the collection. NP swab is the recommended test for suspected COVID-19 as it is safe and well-tolerated by patients.[11–13] However, false negatives (20-40% in NP swab) can occur due to viral load variability throughout stages of the disease, or due to poor technique and this could result in missed diagnosis.[13–16] The positivity of PCR varies depending on the specimens, with higher positive rates on BAL (93%) and sputum (72%) when compared to nasopharyngeal swabs (63%). Despite these findings, in suspected COVID-19 cases, the use of bronchoscopy has been limited, and not recommended routinely, due to the risk it poses to medical staff.[17,18] However, in immunocompromised patients, the diagnosis of COVID-19 can be obscured by other etiologies such as CMV and PJP pneumonia. In such cases, protocols within the institutions on how to perform bronchoscopies safely should be in place; some considerations might include performing BAL immediately after endotracheal intubation. Moreover, as evidenced in this case, highly suspected COVID-19 cases should lead to discussions to safely pursue a diagnosis while also being able to rule out other common causes of respiratory failure in cancer patients.
A chest CT scan has a high sensitivity for COVID-19 and may be considered as a primary tool for COVID-19 detection in highly epidemic areas. Given the lack of clear data regarding the sensitivity of rRT-PCR NP swab in patients with GI manifestations early on in the disease, further study is needed to assess the impact of early chest CT scan on COVID-19-related outcomes.
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