key: cord-0887874-zs86lyxq
authors: Dingemans, Anne-Marie C.; Soo, Ross A.; Jazieh, Abdul Rahman; Rice, Shawn J.; Kim, Young Tae; Teo, Lynette LS.; Warren, Graham W.; Xiao, Shu-Yuan; Smit, Egbert F.; Aerts, Joachim G.; Yoon, Soon Ho; Veronesi, Giulia; De Cobelli, Francesco; Ramalingam, Suresh S.; Garassino, Marina C.; Wynes, Murry W.; Behera, Madhusmita; Haanen, John; Lu, Shun; Peters, Solange; Ahn, Myung-Ju; Scagliotti, Giorgio V.; Adjei, Alex A.; Belani, Chandra P.
title: Treatment guidance for lung cancer patients during the COVID-19 pandemic
date: 2020-05-15
journal: J Thorac Oncol
DOI: 10.1016/j.jtho.2020.05.001
sha: 0baffdf3900302d1a91c63f7a634fff20b34e302
doc_id: 887874
cord_uid: zs86lyxq

Abstract The global COVID-19 pandemic continues to escalate at a rapid pace inundating medical facilities and creating significant challenges globally. The risk of SARS-CoV-2 infection in cancer patients appears to be higher especially as they are more likely to present with an immunocompromised condition, either from the cancer itself or from the treatments they receive. A major consideration in the delivery of cancer care during the pandemic is to balance the risk of patient exposure and infection with the need to provide effective cancer treatment. Many aspects of the SARS-CoV-2 infection remain poorly characterized currently and even less is known about the course of infection in the context of a patient with cancer. As SARS-CoV-2 is highly contagious, the risk of infection directly affects the cancer patient being treated, other cancer patients in close proximity, and health care providers. Infection at any level for patients or providers can cause significant disruption to even the most effective treatment plans. Lung cancer patients, especially those with reduced lung function and cardiopulmonary co-morbidities are more likely to have increased risk and mortality from COVID-19 as one of its common manifestation is as an acute respiratory illness. The purpose of this manuscript is to present a practical multidisciplinary and international overview to assist in treatment for lung cancer patients during this pandemic, with the caveat that evidence is lacking in many areas. It is expected that firmer recommendations can be developed as more evidence becomes available.

In December of 2019, an atypical pneumonia of unknown origin was reported in patients in Wuhan, China. The source was thought to be a wet market called the Huanan Seafood Wholesale Market. Subsequently, it was determined that the agent responsible was an enveloped RNA beta coronavirus, designated Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2, or 2019-nCoV) (1) (Fig. 1) . The condition associated with the SARS-CoV-2 virus was named COronaVIrus Disease 2019 (COVID-19) , and it was designated a pandemic by the World Health Organization (WHO) on March 11, 2020 . Genomic characterization of the virus determined that the agent was distinct from other coronaviruses like SARS-CoV and Middle East Respiratory Syndrome (MERS-CoV) (2) . SARS-CoV-2 is highly infectious. As of May 3, 2020, there were 3.6 million documented cases globally with, 248,000 deaths, resulting in a case fatality rate of 6.9%. However, these numbers are likely to be inaccurate since asymptomatic infections occur and the rate of testing in different countries range from a low of 4 people tested out of 1 million population in Yemen to 146,000 tested out of 1 million population in Iceland (3) . Patients with cancer are at a heightened risk for developing serious complications from COVID-19 (4, 5) . As a group, they tend to be older and have an increased risk of relative immunosuppression from the underlying malignancy and from anti-cancer treatments. Furthermore, patients with lung cancer may have additional comorbidities, including a history of smoking and pre-existing lung disease. There are challenges in the management of a patient with lung cancer given similarities in radiologic findings, respiratory symptoms and presence of underlying immunosuppression. In addition, immune checkpoint inhibitors are now widely used in the management of advanced lung cancer. Immune related pneumonitis from these agents could mimic COVD-19 radiologically. In this article, we aim to provide guidance in the management of lung cancer patients during this period through a multi-disciplinary perspective, based on clinical experience and the available data in the literature.

According to the WHO and Centers for Disease Control and Prevention (CDC), the preferred current diagnostic method is the detection of SARS-CoV-2 nucleic acid in patient specimens (6, 7) . SARS-CoV-2 preferentially proliferates in type II alveolar cells (AT2) and the peak of viral shedding appears 3 to 5 days after the onset of disease. Therefore, an initial negative nucleic acid test does not exclude a positive on subsequent days, as the negative predictive value is relatively low. Appropriate samples include the upper airways (pharyngeal swabs, nasal swabs, nasopharyngeal secretions), the lower airways (sputum, bronchoalveolar lavage fluid specimens), as well as blood, feces, urine and conjunctival secretions. Sputum and other lower respiratory tract specimens have a high positive rate of nucleic acids (8) .

When test material is scarce, the diagnosis and case definition can be made based on clinical symptoms and radiologic characteristic (9) . The WHO has advised every country to establish and publish their case definitions appropriate for their region.

Serologic tests are currently being developed. However, due to a lack of sensitivity of a number of tests, and more importantly, the delay from the time of infection to antibody development, these tests may serve as a useful tool for population-based analysis for epidemiological purposes, while RT-PCR remains the best methodology to detect acute infections,

The main modes of SARS-CoV-2 transmission is through respiratory droplets and contact (10) (11) (12) , whilst airborne transmission may be possible in situations where aerosols are generated, such as endotracheal intubation and during bronchoscopy (13) . The mean incubation period in patients is approximately 4-5.2 days and the mean serial interval, or time between onset of symptoms in one individual and onset in a serial individual, is 7.5 days (14) (15) (16) . Viral load is more similar to influenza and it does not differ between symptomatic and asymptomatic patients (17) . Like SARS-CoV, the SARS-CoV-2 virus appears to use the ACE2 receptor to enter host cells (18) . ACE2 is highly expressed on cells in blood vessels, the heart, the kidney and AT2 cells in the lungs. The latter are important for the synthesis, storage and secretion of surfactant, a substance that prevents atelectasis of lung tissue by lowering surface tension of alveoli. The destruction of AT2 cells may play a key role in the development of severe pulmonary symptoms in patients with COVID-19. It has been shown that the ACE2 receptor is significantly more expressed in chronic obstructive pulmonary disease patients, in current versus former versus never smokers and shows an inverse relationship with forced expiratory volume in 1 second (19) .

Recent reports from China and Italy suggest that approximately 60-90% of patients present with fever, 55-70% with cough, and 33% with dyspnea (20) . Other symptoms including nausea, vomiting, and diarrhea, were observed in < 5% of patients. In the US, the CDC added other symptoms to this list -myalgia, fatigue, headache, sore throat, and new loss of taste or smell Laboratory abnormalities such as lymphopenia (83.2%), thrombocytopenia (36.2%) and leukopenia (33.7%) were observed in hospitalized patients (14) . Radiologic findings will be discussed in a subsequent section.

Approximately 15-20% of patients will develop severe symptoms and may require hospitalization and intensive care. Severe complications may include bilateral pneumonia (75%) acute respiratory distress syndrome (ARDS) (17%) and multiorgan failure (11%) (21) (22) (23) . Emerging data indicate that vascular inflammation can result in diffuse microangiopathy with thrombosis, which contributes to multi-organ failure. In addition, pulmonary embolism, myocardial ischemia and cerebrovascular accidents have been reported (24) ( Table 1) .

Those with the most severe disease upon hospitalization tend to be older and have pre-existing underlying diseases (14, 25) . In 355 patients who died from COVID-19, 70% were men, 30% had ischemic heart disease, 36% had diabetes, 25% had atrial fibrillation, and 20% had cancer (26) . Only 0.3% had no preexisting diseases.

Patients with a higher Sequential Organ Failure Assessment (SOFA) score and ddimer greater than 1 ug/ml were found to be at higher risk for death from COVID-19 (25) . Any potential relationship between the smoking status of the patients and the onset/severity of the disease remains unknown.

The primary aim of diagnosis in a patient with suspected lung cancer is to obtain tissue specimens for histological diagnosis, using the least invasive method. But the risk of spreading SARS-CoV-2 infection needs to be considered. In addition there is a risk of slow-down of diagnostic procedures as patients are afraid of going to the hospital during the current pandemic. Bronchoscopy, an aerosol generating procedure, should be avoided whenever possible.

The American Association for Bronchology and Interventional Pulmonology has issued a statement on the safe and effective use of bronchoscopy in patients with suspected or confirmed COVID-19 (27). The following applies to suspected and confirmed patients with lung cancer.

• Elective Bronchoscopy for lung mass, bronchial mass, mediastinal or hilar lymphadenopathy, lung infiltrates and mild to moderate airway stenosis should be postponed until after full recovery from COVID-19.

• Bronchoscopy for urgent/emergent reasons should be considered with all precautionary measures only if it is a lifesaving intervention, e.g., massive hemoptysis, benign or malignant severe airway stenosis or suspicion of an alternative or secondary infectious etiology or malignant condition with resultant significant endobronchial obstruction or rapidly progressing malignancy The Society of Interventional Radiology has categorized all procedures such as transthoracic needle biopsies as elective, urgent, and emergent (28) . Procedures that can be delayed/rescheduled in cases of worsening local infection rates should be determined on an individual basis.

Pathologically, in the early and pre-symptomatic phase, the lungs exhibit exudation of proteinaceous fluid, mixed with patchy inflammatory cellular infiltrates and focal reactive hyperplasia of type II pneumocytes. Although patchy alveolar epithelial injury can be seen, hyaline membrane formation, a pivotal feature of diffuse alveolar damage, is not evident (29) .

In severe and fatal cases, limited gross findings from autopsy studies have shown large areas of lung consolidation and hemorrhage, with mucus plugs evident in small airways (30) . Damage to alveolar epithelial cells with desquamation and mononuclear inflammatory cell infiltration in airspaces has been observed (31, 32) .

Thin to quite prominent hyaline membranes, hyperplasia of type II pneumocytes, congestion of septal capillary vessels, and microthrombi are also commonly seen (31, 33) . In addition to these changes of ongoing diffuse alveolar damage (DAD), alveolar hemorrhage and consolidation by fibroblastic proliferation with extracellular matrix and fibrin forming clusters in airspaces can be prominent (31, 33) . Others have observed mucous plugs in the alveoli and bronchioles and the activation of alveolar macrophages (34) . In some patients, consolidation consisted of abundant intra-alveolar neutrophils, consistent with superimposed bacterial bronchopneumonia (31) .

Several studies have suggested the presence of fibrosis in lungs of COVID-19 patients (33, 34) . However, it appears this mainly corresponds to microscopic findings of fibroblast proliferation with early extracellular matrix production in small airways and airspaces, with thickened alveolar walls and interstitial areas with increased stromal cells and CD4+ lymphocytes (31) (32) (33) . Whether or not true pulmonary fibrosis occurs in COVID-19 patients will depend on longitudinal follow up of the long-term survivors, especially when symptoms appear, and biopsies when indicated, are examined.

In summary, based on limited data currently available, the basic underlying pathology of COVID-19 pneumonia appears to be that of diffuse alveolar damage (DAD), with varying degrees of organization. Additionally, embolic events are frequent with vascular damage.

Typical chest X-ray (CXR) radiographic features of COVID-19 patients include consolidation with limited cases of pleural effusion (35) . Chest radiographs are less sensitive in the detection of COVID-19 with a sensitivity of around 30-70% (36) .

However, with the current limitations in diagnostic availability and kit performance, the total positive rate of reverse transcription polymerase chain reaction (RT-PCR) from nasopharyngeal swabs has been reported to be 59% at initial presentation (37) .

It is in this setting that European radiologists have utilized diagnostic algorithms to evaluate the use of first line triage diagnostic CXR (35) .

The Radiological Society of North America (RSNA) has recently published an Expert Consensus Statement on Reporting Chest CT Findings Related to COVID-19 (38) .

This attempts to categorize CT findings of COVID-19 pneumonia into typical, indeterminate, atypical appearances and negative for pneumonia (38) . 2) Progressive stage: 5-8 days after onset of symptoms; peripheral focal or multifocal GGO affecting both lungs in approximately 50-75% of patients, which then rapidly develop into crazy paving pattern and areas of consolidation, typically affecting both lungs (Figure 2b) .

3) Peak stage: 9-13 days after onset of symptoms; as the disease progresses, crazy-paving and consolidation with air bronchograms become the dominant findings (Figures 3a and b) .

These stages are then followed by a slow clearing starting approximately at (but not before) one month post-symptoms. The reported sensitivities of CT images for COVID-19 were 60% to 98%, but had a low specificity (25% to 53%) (42) . CT features such as bilateral involvement, peripheral distribution and lower zone dominance can also be assessed on CXR (35) .

A non-contrast CT scan is recommended as IV contrast may mask subtle GGO (39) .

Axial reconstruction should be performed without gap on 0.625 to 5 mm axial slice thickness depending on institutional logistics, data storage and processing capabilities.

Atypical CT findings are only seen in a small minority of patients and should raise concern for superimposed bacterial pneumonia or other differential diagnoses (40): mediastinal lymphadenopathy, pleural effusions, multiple tiny pulmonary nodules, tree-in-bud opacities, and cavitation. Pneumothorax and the halo-sign are also rarely seen (21, 43) .

The American College of Radiology does not recommend the use of CXR or CT for screening of COVID-19 in patients without symptoms as imaging findings are not specific and may overlap with those of other infections and acute lung injury manifesting as organizing pneumonia pattern from drug toxicity, connective tissue disease or idiopathic causes (42, 44) . However, in symptomatic patients with a high suspicion of COVID-19, but negative PCR, CT scan may make the diagnosis much more likely, especially in individuals without pulmonary comorbidities.

GGO and consolidation in COVID-19 could mimic radiotherapy-or chemotherapy/immunotherapy-associated pneumonitis and viral infections, although they tend to be more peripheral. The chemotherapy/immunotherapy-associated pneumonitis appear to be more confluent and perihilar (45) . In addition, CT findings suspicious for COVID-19 may be incidentally encountered in lung cancer patients at the time of diagnosis (Fig. 2a) or post-treatment. In such situations, the risk of infection should be evaluated by a multidisciplinary team including clinicians and radiologists, along with history and the consideration of RT-PCR testing.

It is also important to highlight that CT pulmonary angiography might represent a valuable tool for detection of pulmonary thrombo-embolism (TEP) and subsequent management in patients with COVID pneumonia: in fact, elevated D-dimer and TEP is thought to be a common laboratory finding in these patients, especially those with severe lung damage (46) . 

Currently, there is no specific validated treatment for COVID-19, and management comprises of supportive/symptomatic care, and instituting recommended infection prevention and control measures. There are anecdotal reports as well as pre-clinical data supporting investigation of potentially efficacious drugs (47) . A number of these including chloroquine and its analogs with or without azithromycin, antivirals such as remdesivir (developed against Ebola but found to be ineffective), lopinavir/ritonavir (anti-HIV), and monoclonal antibodies against IL-6 [tocilizumab (48) ] are currently being studied in clinical trials globally. Multiple studies are also evaluating the use of convalescent plasma in patients with severe COVID-19 ( Table 2) .

Results from a few studies have been reported. A study from China that randomized 237 symptomatic patients in a 2:1 ratio to remdesivir or placebo found that remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87-1·75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95-2·43]) (49) . On the other hand, interim results after DSMB mandated unblinding of a randomized, placebo-controlled trial involving 1063 hospitalized patients with advanced COVID-19 and lung involvement, showed promising results.

Patients who received remdesivir had a 31% faster time to recovery than those who received placebo (p<0.001). Specifically, the median time to recovery was 11 days for patients treated with remdesivir compared with 15 days for those who received placebo. Results also suggested a non-statistically significant survival benefit, with a mortality rate of 8.0% for the group receiving remdesivir versus 11.6% for the placebo group (p=0.059) (50) . This study conducted by the US National Institutes of Health has not been published in the peer-reviewed literature yet, thus the results are considered preliminary. However, the US FDA on May 1 st , 2020 granted emergency approval to remdesivir for the treatment of patients with severe COVID-

The major goal of lung cancer management during the COVID-19 pandemic is to minimize the risk of exposing the patient and staff to infection, while managing all life-threatening aspects of their disease. This can be achieved by limiting face-to-face visits with providers and visits to the clinic or hospital, whenever possible. Patients who need to physically come to the hospital need to be screened for symptoms and tested for SARS-CoV-2 infection if there are any of the typical symptoms discussed above and in Table 1 .

Whenever possible, patients undergoing any invasive procedure or systemic chemotherapy/immunotherapy should be tested for Covid-19 infection.

Overall clinical trial accrual in general has slowed down during the pandemic. New patient accrual has been put on hold at various institutions temporarily. We 

The treatment of locally advanced lung cancer could involve surgery, radiotherapy, and systemic therapy, but most patients with stage III NSCLC will be treated with combined concurrent chemoradiotherapy typically consisting of platinum-based chemotherapy with radiotherapy delivered as 60 Gy in 30 fractions (61) followed by consolidation durvalumab (62) . As the aim of treatment is curative, the decision for treatment will need to take into consideration factors including the risk of developing COVID-19, the risk of developing treatment-related toxicities, and the availability of resources to administer treatment safely. At this time, the relationship between SARS-CoV-2 infection and severity with chemotherapy, radiotherapy, or immunotherapy has not been clearly defined but it has been reported that anticancer therapy within 14 days of COVID-19 diagnosis was associated with an increased risk of developing severe complications (21) . On the other hand, this was not confirmed in the most recent larg series (63) (64) (65) . Careful consideration should be Though alternative chemoradiotherapy treatment schemes exist (58), themes for treatment remain largely consistent: patients must come to clinic once a day, 5 days per week, for several weeks. This requires daily contact with other patients, treating staff, and transportation to the clinic, which all represent contact modes for infection over a prolonged treatment period.

An alternate approach is the use of hypofractionation to decrease the number of radiotherapy fractions. If clinical resources are strained or if exposure risk is high, radiotherapy could be delayed but at the risk of increased mortality (68), so risks and benefits need to be discussed among the treatment team and patient. The contemporary use of alternative fractionation schemes combined with chemotherapy and immunotherapy in the curative setting has not been tested (69) . Alternative fractionations could include 55 Gy in 20 fractions with reasonable toxicity profiles (70, 71) . Sequential chemotherapy followed by radiotherapy could be considered but would expose patients to a prolonged course of cancer treatment during an ongoing pandemic.

As discussed previously, SARS-CoV-2 infection may induce radiological abnormalities similar to radiation induced pneumonitis or immunotherapy induced pneumonitis. In a patient treated with chemo-radiation or an immune checkpoint inhibitor, presentation with dyspnea and radiological evidence of pneumonitis can often provide a diagnostic challenge. In this situation, after appropriate investigations, corticosteroid treatment may be considered for patients who have been tested negative for COVID-19.

However, the development of new infiltrates during radiotherapy was shown in a case report to precede COVID-19 symptoms and confirmed infection by 3 days (72).

Radiation oncologists can review daily radiotherapy imaging to ascertain if any new infiltrates develop and this may prove to be useful for early detection. Based on current sparse data, it is hard to predict how checkpoint blockade will influence SARS-CoV-2 infection. There is an urgent need to collect data from patients with COVID-19 who are on checkpoint inhibitor treatment. Recently a worldwide initiative TERAVOLT (Thoracic cancERs international coVid 19 cOLlaboraTion) has been instituted to collect these data (63, 79) . The first analysis done on 200 patients with thoracic cancers suggested that the overall mortality rate in thoracic malignancies is 34.6%. However, many patients were not admitted to intensive care units. With the present analysis, it seems that there is no detrimental effect of immunotherapy on the outcome of COVID-19 compared to other treatments.

In addition, multivariable analysis failed to show that comorbidities were associated with an increased risk of death. For this reason, it is impossible to identify a category of patients with thoracic cancer at higher risk to have a severe course of COVID-19.

Therefore, prevention remains the only safeguard for these patients.

The use of molecular targeted therapy, immunotherapy and chemo-immunotherapy in advanced NSCLC has resulted in long term survival in a proportion of patients.

Thus, the decision to initiate or interrupt treatment poses a challenge for both the patient and their physicians. As lung cancer related symptoms are similar to COVID-19, a careful history and examination is essential prior to treatment in order not to miss COVID-19 infection. All patients and health care providers should follow the general measures described in previous sections to minimize exposure and to reduce side effects. Response evaluation can be deferred from every 2 cycles to 3 or 4 cycles to reduce the frequency of hospital visits, provided patients are clinically stable. Radiological findings of SARS-CoV-2 infection are difficult to differentiate from drug-induced pneumonitis or immune related pneumonitis, where a GGO pattern is dominant. Thus, every patient with suspicious radiological findings must be evaluated with a SARS-CoV-2 test.

Many patients at initial diagnosis may require immediate therapy and should be treated according to institutional guidelines. However, whenever possible, particularly in high risk patients such as those who are frail, elderly or with comorbidities, treatment should be delayed if the tumor burden is low. All decisions should be discussed with the patient and family. Regimens with low myelosuppressive potential are preferred, and the use of GCS-F should be utilized as needed, notwithstanding the standard guidelines.

For non-squamous carcinoma with high PD-L1 expression, single agent pembrolizumab is preferred to a chemotherapy/PD1/PD-L1 combination to reduce the incidence of hematological or other side effects. Given concerns about the interaction of checkpoint inhibitors with COVID-19 and the lack of data as guidance, in specific cases, it is reasonable if the use of pembrolizumab is deferred and systemic chemotherapy alone is administered. For pemetrexed treatment, doses of dexamethasone can be reduced to minimize immunosuppression.

Similar to non-squamous carcinoma, for squamous carcinoma with high expression of PD-L1, pembrolizumab is preferred to a chemotherapy/PD1/PD-L1 combination to reduce the incidence of hematological or other side effects. If a chemotherapy combination is used, an effort should be made to utilize the least myelosuppressive regimen.

For patients on single agent immunotherapy, a number of approaches have been proposed to minimize the risk of infection. One recommendation is to continue treatment for patients in the early induction phase or short-term maintenance phase of therapy. In these patients, every attempt should be made to limit the number of In patients who have been on therapy for over a year, consideration could be given to deferring treatments for even longer periods. Steroids should be avoided as much as possible. Preliminary results of TERAVOLT suggest that these patients have a risk of long hospitalization, compared to those with other treatments.

SCLC is a highly aggressive disease and is characterized by a rapid response to chemotherapy. Postponing first line treatment will therefore rarely be possible. For patients with limited disease SCLC the standard treatment is concurrent chemoradiotherapy where radiotherapy is given twice daily for three weeks or once daily for 6 weeks with comparable disease control and toxicity outcomes (81) . A shortened treatment time would facilitate optimal care with decreased total time of SARS-CoV-2 exposure risk. The CONVERT trial has demonstrated that with modern radiotherapy techniques severe radiotherapy induced toxicity is limited, however more than 70% of patients experience grade 3-4 neutropenia (81) . Dose reductions should be considered and in patients expected at high risk for both neutropenia and COVID-19, i.e. frail, elderly, hypertension, sequential chemoradiotherapy should be considered. Given the relatively modest benefit of prophylactic cranial irradiation and consolidative radiotherapy, it has been suggested that both can be removed from care patterns (82) . It is also suggested that oral etoposide could be considered an option for SCLC patients during COVID-19, to reduce the frequency of hospital/clinic visits.

For decades the standard treatment of patients with metastatic SCLC was etoposide-platinum. Recently, improved PFS and OS have been shown when atezolizumab was added to chemotherapy (83) . However, the improvement in outcome is modest and no predictive biomarker is available to select patients who will benefit. It is therefore reasonable to omit atezolizumab in patients at high risk of COVID-19 mortality, described previously. When utilized, a less frequent schedule with every four weeks of atezolizumab should be considered. The use of G-CSF or dose reductions of the chemotherapy regimen in patients at high risk of neutropenia should be considered. Second and further line treatment should be postponed after a full discussion with patients and family based on the risk/benefit ratio.

The rapid onset of the COVID-19 pandemic requires careful consideration of urgent decisions to treat lung cancer by oncologists. Treatment decisions balancing risk of exposure with effective care requires close multidisciplinary discussions and thorough deliberation between caregivers and patients. The duration and severity of the COVID-19 pandemic is unclear, and treatment delay alone will be insufficient to provide optimal treatment to cancer patients. In combination with determining a treatment path for lung cancer, physicians should educate patients to help them prevent further spread of COVID-19 according to WHO and CDC guidelines.

Patients who commit to treatment should further commit to self-isolation and safe practices for themselves, other patients, and providers.

COVID-19 will eventually be controlled. However, outbreaks are likely to recur. To be prepared, a number of the international COVID study groups have been organized, and active participation is encouraged.

The authors wish to acknowledge the expert secretarial, administrative and editorial support provided by Vun-Sin Lim, PhD. (Fig 3a) and lungs (Fig 3b) of a 54-year-old Chinese male patient day 13 of onset of symptoms demonstrate large bilateral pleural effusions with dense dependent consolidation at the lower lobes (arrows). Trivial pericardial effusion (arrowhead). Partially imaged extracorporal membrane oxygenation (ECMO) catheter overlying the right anterior chest wall. Stereotactic body radiation therapy, SBRT 

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