The optimal clinical management of COVID-19 patients is largely debated, as well as the treatment aimed for a specific subset of patients, such as cancer patients or the ones at risk for thrombosis. Several doubts and curiosities of this regard have arisen among patients and healthcare professionals.
We asked Professor Khorana, an expert in cancer and cancer-associated thrombosis and member of our editorial board, a series of questions to help us through the understanding of COVID-19 in these specific settings.
Professor Khorana, are cancer patients more susceptible to infection? Does chemotherapy increase the risk of infection due to a resulting immunosuppressive state?
“In general, it has previously been well-established that cancer patients – particularly those on myelosuppressive therapy – are more susceptible to infection.”
Is there a tumor type or a specific tumor therapy that is considered at higher risk for infection?
“Myelosuppressive regimens, such as stem cell transplants, are associated with higher risk for infection.”
Do cancer patients have a poorer prognosis with COVID-19?
“The data regarding risk and outcomes of cancer patients with COVID-19 are still limited but it appears that some cancer patients are at risk for a worse prognosis. Most of these data are from China and they appear to disproportionately include older patients, patients with lung cancer and smokers, therefore, it is unclear if this applies to all cancer patients. In the absence of extensive data, however, safety should be a priority when assessing risk/benefit of anti-cancer therapy.”
For a cancer patient who is positive for SARS-CoV-2 infection, is it advisable to postpone or change the ongoing therapy for cancer?
“Current guidance across various countries recommends holding treatment for cancer in patients who are positive for SARS-CoV-2 infection for at least 14 days, assuming resolution of all symptoms. If testing is widely available, negative testing for SARS-CoV-2 should be established before resuming anti-cancer therapy.”
Can SARS-CoV-2-induced pneumonia worsen the outcome for cancer patients? In case of recovery from COVID-19, will the lungs be weaker and functional? Will the lungs sustain a cancer treatment after recovery from COVID-19?
“Long-term outcomes of SARS-CoV-2-induced pneumonia are not fully understood but it definitely appears to lead to subacute/chronic issues in some patients. Such decisions have to be made on a case-by-case basis.”
SARS-CoV-2 infection is associated with prolonged coagulation profile and increased level of D-dimer. Would patients who are already on antiplatelet drugs and have been diagnosed with COVID-19, be protected from coagulation-associated adverse events? Or would COVID-19 exacerbate coagulation disorders?
“An effect of SARS-CoV-2 infection on coagulation profile has been noted both anecdotally and in limited published reports. Anecdotal reports of sudden death and asystole during recovery from SARS-CoV-2 infection have brought up the possibility of pulmonary embolism as a cause. Urgently issued ISTH guidelines recommend that ALL patients (not just the critically ill) admitted with COVID-19 infection should be considered for prophylactic anticoagulation, assuming no active bleeding, risk for bleeding, severe thrombocytopenia (platelet counts <25,000) or other contraindications. Thankfully, bleeding appears to be rare in patients with COVID-19 infection.”
Are these effects on coagulation characteristic only of the severe infection or also of the milder form?
“It appears that effects on coagulation occur in milder forms of COVID-19 infection, although not to the same degree. In a large analysis of over 1000 patients from China, D-dimer ≥0.5 mg/l was noted in 43% of patients with non-severe disease and 60% with severe illness (1).”
For a patient under anticoagulation therapy who is positive for SARS-CoV-2 , is there a rationale to change or adjust the therapy?
“There are currently no recommendations to change anticoagulation therapy during COVID-19 infection unless new bleeding risks appear. As noted, bleeding appears to be a rare event with this infection.”
The antiplatelet dipyridamole has been suggested as a possible therapy for improving COVID-19-elevated D-dimer levels. Is this agent also suggested for patients already on an antiplatelet regimen? Can this potential treatment have adverse events for these patients?
“There are promising data for dipyridamole, but the evidence is not strong enough to recommend for patients outside of a clinical trial.
Some studies report that heparan sulfate binds Coronavirus surface proteins used by the virus for its attachment to target cells (2). The closely related glycosaminoglycan heparin could be proposed as a therapeutic antiviral agent to interfere with the virus binding to the cell and, therefore, prevent infection.
In the light of the already known safety profile of heparin, would you consider the use of heparin/heparan sulfate as an antiviral agent in the treatment of SARS-CoV-2-positive patients? Would you expect any adverse events in terms of bleeding?
“These are important research questions, but such approaches should not be adopted outside of a defined research protocol. In a study under submission by Tang et al., described in the ISTH guidance document (3), no difference in mortality was observed in patients receiving prophylactic LMWH or not; however, for patients with high sepsis-induced coagulopathy scores, LMWH therapy was associated with improved mortality.”
Children are apparently less prone to develop a severe form of COVID-19 in comparison to adults. Is that also true for children who suffer from an existing tumor?
“Thankfully, COVID-19 does not seem to substantially affect pediatric patients. Given the rarity of pediatric cancer, there are not good data to evaluate risk but all precautions must be followed to protect children with pediatric malignancies given that they are generally immunosuppressed.”
What about the psychological support for cancer patients? The SARS-CoV-2 pandemic may have increased the worries and need for emotional support of these patients who may feel weaker to face this new uncertain situation. Do you have any evidence of increased anxiety among cancer patients?
“Given the rapidly evolving pandemic, there are not a lot of studies regarding increased anxiety and distress in cancer patients related to SARS-CoV-2 but anecdotally this has certainly been noted.”
We are truly thankful to Professor Khorana for the time he dedicated to promptly answer our questions in such a crucial moment for patient healthcare.
References
- Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020. DOI: 10.1056/NEJMoa2002032. Epub ahead of print.
- Milewska A, Zarebski M, Nowak P, et al. Human Coronavirus NL63 utilizes heparan sulfate proteoglycans for attachment to target cells. J Virol 2014;88(22):13221-13230.
- Thachil J, Tang N, Gando S, et al. ISTH interim guidance on recognition and management of coagulopathy in COVID‐19. J Thromb Haemost 2020. doi: 10.1111/jth.14810. [Epub ahead of print].