key: cord-0871348-zgtbtwvq
authors: Padala, Sandeep A.; Medepalli, Vidya M.; Mohammed, Azeem; Vakiti, Anusha; Elam, Rachel; Gupta, Sandeep J.
title: Management of Immunosuppression During Severe COVID-19 Infection in a Patient With Pulmonary and Cardiac Sarcoidosis
date: 2020-07-17
journal: J Clin Rheumatol
DOI: 10.1097/rhu.0000000000001557
sha: b7c9de760426744048773b8e617de3a2ecfc4490
doc_id: 871348
cord_uid: zgtbtwvq

nan

reaction test following low-grade fevers, cough, and myalgias and was recommended to self-isolate. Her home medications included 20 mg methotrexate weekly, 40 mg subcutaneous adalimumab every 14 days, 40 mg prednisone daily, mexiletine, and amiodarone. Because of a positive COVID-19 result, methotrexate and adalimumab were held, and prednisone was continued. Vital signs on admission were a temperature of 37.8°C, heart rate 102 beats/min, blood pressure 105/75 mm Hg, respiratory rate 22 breaths/ min with oxygen saturation of 92% on 2 L via nasal cannula, and body mass index of 34.3 kg/m 2 . At baseline, patient had normal oxygen saturation >95% on room air. On physical examination, she was in minimal respiratory distress with use of accessory muscles but no cyanosis. Lung examination revealed symmetrical expansion with faint crackles bilaterally. The cardiovascular examination revealed regular rhythm and no edema. The laboratory values and trends are shown in the Table. An anteroposterior chest radiography ( Fig. 1 ) was performed and showed mild pulmonary vascular congestion but was negative for consolidations or infiltrates.

She was initially admitted to the medical floor, and overnight, the oxygen requirement increased from 2 to 4 L via nasal cannula. Given the leukocytosis, blood cultures were obtained, and empiric ceftriaxone was started. Patient had persistent fever with peak temperature of 39.5°C. Along with the antibiotics, oral hydroxychloroquine was initiated starting with 400 mg for 2 doses every 12 hours followed by 200 mg every 12 hours for 5 days for COVID-19 infection. Given the baseline cardiac history and use of antiarrhythmic agents, azithromycin was not used because of concern for prolonging the QT interval. Approximately 36 hours following hospital admission, patient had worsening respiratory distress with increasing oxygen requirement and the need for nonrebreather and transfer to the intensive care unit for mechanical ventilation. A subsequent chest x-ray film ( Fig. 2) showed the development of bilateral pulmonary infiltrates and a slight progression in vascular congestion. Shortly following intubation, patient had hypotension necessitating vasopressors. A single dose of tocilizumab 400 mg intravenously was given at this time because of progression to severe COVID-19 infection requiring mechanical ventilation and vasopressors. Prednisone was continued as a concern for adrenal crisis related to long-term steroids. Rheumatology recommended holding methotrexate and adalimumab and continuing only the prednisone. Over the next 6 days, the vasopressors were weaned off, and she was successfully extubated and discharged home in stable condition without any oxygen requirement. Our case emphasizes the challenges in managing immunosuppressed patients with COVID-19 infection and also describes the importance of managing the immunosuppression. The most important thing is to cut down the immunosuppressive therapy carefully to treat the infection and simultaneously to avoid the flare-up of the underlying disease ( Figs. 3 and 4) .

The emergence of the 2019 novel coronavirus is particularly worrisome for people with sarcoidosis, not only because of these patients' already weakened immune system but also because of the symptoms of COVID-19, such as fever, cough, sore throat, and difficulty breathing, can mimic worsening of sarcoidosis. Among the general population, the case fatality rate was 2.3%, whereas it was as much higher for people with preexisting comorbidities such as 10.5% for cardiovascular disease, 7.3% for diabetes, 6.3% for chronic respiratory disease, 6.0% for hypertension, and 5.6% for cancer. 1 The US Centers for Disease Control and Prevention has patients with underlying comorbidities such as preexisting lung conditions under the category of high risk to acquire the infection. 2 To the best of our knowledge, this is the first case reported of COVID-19 infection in a patient with sarcoidosis reported in the literature. The exact mechanism triggering the flare-ups of sarcoidosis or interstitial lung disease (ILD) is not clear, and it could be attributed to underlying infections or idiopathic. 3 The data on COVID-19 causing any flare-ups in patients with preexisting lung conditions are unclear at this stage, and there is a concern that it can flare up in patients with underlying fibrosis due to sarcoidosis. 4 The mechanism of action of the immunosuppressive medications is by affecting both innate and acquired immunity or T and B cells along with the functioning of neutrophils, thus predisposing individuals to a greater risk of infections. 4 Our patient was chronically immunosuppressed and has been on maintenance methotrexate, adalimumab, and a tapering dose of prednisone. The inflammation is prominent and is associated with a myriad of adverse outcomes such as acute lung injury and acute respiratory distress syndrome in patients with COVID-19. Pulmonary histology from patients revealed inflammation and diffuse alveolar damage. 5 Corticosteroids suppress lung inflammation but also inhibit immune responses and pathogen clearance. Studies have shown that steroids prolonged viral shedding in patients infected with SARS and Middle East respiratory syndrome. 5 Therefore, extreme caution has to be exercised prior to prescribing steroids, as steroids are the cornerstone in patients with a history of chronic obstructive pulmonary disease or asthma or ILD. 6 The treatment for the COVID-19 is symptomatic, including self-isolation to oxygen supplementation, mechanical ventilation, extracorporeal membrane oxygenation, use of hydroxychloroquine, azithromycin, tocilizumab, remdesivir, and convalescent plasma. 6, 7 Additionally, drugs such as tocilizumab, a recombinant humanized antihuman interleukin 6 (IL-6) receptor monoclonal antibody, could be of great help in patients with severe COVID-19. This is due to the drug's mechanism of targeting the IL-6 pathway by binding to the IL-6 receptor with high affinity. 7 Through this action, it renders IL-6 incapable of immune damage to target cells and thereby alleviates the inflammatory response responsible for much of the disease. In a study involving patients with severe and critical COVID-19, 7 tocilizumab showed promise. The clinical data from this study showed that the typical coronavirus symptoms, hypoxemia, and computed tomography (CT) opacity changes were improved immediately after treatment with tocilizumab in most of the patients, which suggests that this drug could be an efficient therapy for the treatment of severe COVID-19.

The current case describes a patient who developed COVID-19 in the setting of stage I pulmonary sarcoidosis and cardiac sarcoidosis on chronic multiple immunosuppressive therapies and was successfully managed by withholding the methotrexate and adalimumab and by continuing the prednisone and symptomatic treatment. Recently, on April 29, 2020, Mikuls et al. 8 published American College of Rheumatology guidelines for the management of rheumatologic diseases during the COVID-19 pandemic, and it has been suggested that glucocorticoids should not be abruptly stopped, regardless of exposure or infection status (high level of task force consensus). Regardless of COVID-19 severity, antimalarial therapies (hydroxychloroquine/ chloroquine) may be continued, but sulfasalazine, methotrexate, leflunomide, immunosuppressants, non-IL-6 biologics, and JAK inhibitors should be stopped or held (moderate to high level of task force consensus). 8 Methotrexate, in particular, can cause a pneumonitis and accelerate ILD; thus, it was particularly important to hold it in this patient with COVID-19 pneumonia and underlying stage I pulmonary sarcoidosis who was on relatively high-dose methotrexate.

Despite her underlying cardiac and pulmonary comorbidities requiring chronic immunosuppressive therapy, she recovered from her illness and was discharged home. Although prednisone has been reported to cause immunosuppression and may prolong the duration of viral shedding, because of its anti-inflammatory properties and in combination with the tocilizumab, it may have been helpful in suppressing the systemic inflammation already present with the sarcoidosis and exacerbated with SARS-CoV-2, thereby allowing recovery to ensue for this patient. Because our patient was simultaneously treated with ceftriaxone empirically for community-acquired pneumonia, it is a possibility that her clinical improvement was due to treatment of a superimposed bacterial pneumonia. However, we favor that our patient's respiratory failure and critical illness were secondary to COVID-19 pneumonia alone due to her positive SARS-CoV-2 polymerase chain reaction testing prior to admission, typical COVID-19 presenting symptoms, short duration between hospital admission and respiratory decompensation, negative bronchoalveolar lavage at the time of intubation, and negative blood cultures. A CT scan of the chest was not performed in this case. Both COVID-19 pneumonia and non-COVID-19 pneumonias most often demonstrate ground-glass opacities and/or consolidations on chest CT, and chest CT has a low specificity of 25% for COVID-19 pneumonia, 9 making it unlikely to have changed management in this case.

As the innate immune system is responsible for host tissue damage, 4 whether the coronavirus infection will cause severe to critical illness in the immunosuppressed patients needs to be investigated. As the mortality rate is more than 50% during the ILD flare-ups, it is of utmost importance to diagnose these patients earlier in the disease process and treat them appropriately. 7,10 CONCLUSIONS Infection with SARS-COV-2 can vary widely from an asymptomatic course to mild, severe, or critical illness. The overall morbidity and mortality are much higher in patients with known comorbidities such as coronary artery disease, diabetes, hypertension, cancer, and autoimmune diseases. For patients with comorbidities requiring long-term immunosuppressive therapy, such as those with autoimmune diseases, a multidisciplinary approach is of utmost importance. Further studies are needed to identify the best management options for patients on chronic immunosuppressive therapy.

• Lower threshold to admit patients with underlying history of immunosuppression. • Cardiac sarcoid is a leading cause of death in sarcoidosis, and the frequency of cardiac relapse is high and may be life-threatening.

Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention

Coronavirus disease 2019 (COVID-19): people who are at higher risk for severe illness

Community acquired respiratory and gastrointestinal viral infections: challenges in the immunocompromised host

Coronaviruses and immunosuppressed patients: the facts during the third epidemic

Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury

Patients with interstitial lung disease and pulmonary sarcoidosis are at high risk for severe illness related to COVID-19

Effective treatment of severe COVID-19 patients with tocilizumab

American College of Rheumatology guidance for the management of rheumatic disease in adult patients during the COVID-19 pandemic: version 1

Correlation of chest CT and RT-PCR testing in coronavirus disease 2019 (COVID-19) in China: a report of 1014 cases

Acute exacerbation of idiopathic pulmonary fibrosis: incidence, risk factors and outcome