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Letter| Volume 135, ISSUE 6, e137-e138, June 01, 2022

Comments on COVID-19 and AL Amyloidosis, the Missing Links

DOI:https://doi.org/10.1016/j.amjmed.2022.02.011
Comments on COVID-19 and AL Amyloidosis, the Missing Links
Previous ArticleCOVID-19 and Light Chain Amyloidosis: Correspondence
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      To the Editor:
      Crees and Stockerl-Goldstein
      • Crees ZD
      • Stockerl-Goldstein K
      COVID-19 and light chain amyloidosis, adding insult to injury [online ahead of print].
      Am J Med. 2022 January 23; https://doi.org/10.1016/j.amjmed.2022.01.005
      recently reviewed the management of light chain (AL) amyloidosis during the coronavirus disease 2019 (COVID-19) pandemic. While the literature discussed by authors is pertinent, certain lacunae in the diagnosis, prevention, and management need attention.
      Monoclonal protein in AL amyloidosis could be secreted by either plasma cells or, rarely, B-cells.
      • Jain A
      • Haynes R
      • Kothari J
      • Khera A
      • Soares M
      • Ramasamy K
      Pathophysiology and management of monoclonal gammopathy of renal significance.
      Blood Adv. 2019; 3: 2409-2423
      In addition to direct organ toxicity due to tissue deposition, monoclonal protein could cause 1) immunoparesis leading to increased risk and severity of infections, and an impaired vaccination response; and 2) coagulation disturbance leading to bleeding, thrombosis, or reduced antithrombin levels.
      • Jain A
      • Ramasamy K
      Potential 'significance' of monoclonal gammopathy of 'undetermined significance' during COVID-19 pandemic.
      Blood Cells Mol Dis. 2020; 85102481
      COVID-19 has been associated with a potent thrombo-inflammatory milieu that causes thromboembolic complications.
      • Jain A
      • Ramasamy K
      Potential 'significance' of monoclonal gammopathy of 'undetermined significance' during COVID-19 pandemic.
      Blood Cells Mol Dis. 2020; 85102481
      An overlapping multiorgan involvement in AL amyloidosis and COVID-19 has several implications with respect to the drug administration.
      • Jain A
      • Ramasamy K
      Potential 'significance' of monoclonal gammopathy of 'undetermined significance' during COVID-19 pandemic.
      Blood Cells Mol Dis. 2020; 85102481
      In light of these observations and the current evidence, additional points are addressed below:
      • 1.
        Diagnostic challenges for AL amyloidosis during COVID-19.
      • 2.
        Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) booster vaccination in patients with AL amyloidosis.
      • 3.
        Management of indolent B-cell non-Hodgkin lymphoma-associated AL amyloidosis during the COVID-19 pandemic.
      • 4.
        Management and response assessment in patients with AL amyloidosis infected with COVID-19.
      • 5.
        Toxicity consideration of anti-COVID drugs in patients with AL amyloidosis.
      • 6.
        Therapeutic implications of coagulation derangement of the 2 disorders.
      These points are discussed in the Table
      • Jain A
      • Ramasamy K
      Potential 'significance' of monoclonal gammopathy of 'undetermined significance' during COVID-19 pandemic.
      Blood Cells Mol Dis. 2020; 85102481
      , 
      • Avivi I
      • Luttwak E
      • Saiag E
      • et al.
      BNT162b2 mRNA COVID-19 vaccine booster induces seroconversion in patients with B-cell non-Hodgkin lymphoma who failed to respond to two prior vaccine doses.
      Br J Haematol. 2022; 196: 1329-1333
      , 
      • Kalil AC
      • Patterson TF
      • Mehta AK
      • et al.
      Baricitinib plus remdesivir for hospitalized adults with Covid-19.
      N Engl J Med. 2021; 384: 795-807
      , 
      • Jayk Bernal A
      • Gomes da Silva MM
      • Musungaie DB
      • et al.
      Molnupiravir for oral treatment of Covid-19 in non-hospitalized patients.
      N Engl J Med. 2022; 386: 509-520
      under 3 heads: 1) management of AL amyloidosis during COVID-19 pandemic; 2) management of AL amyloidosis in patients with COVID-19; and 3) management of COVID-19 in patients with AL amyloidosis.
      TableA Summary of Additional Management Considerations of AL Amyloidosis During COVID-19 Pandemic
      Management of AL Amyloidosis During COVID-19
      Comment (s)Suggestion (s)
      Prevention measures
       Prophylactic drugs
      • Jain A
      • Ramasamy K
      Potential 'significance' of monoclonal gammopathy of 'undetermined significance' during COVID-19 pandemic.
      Blood Cells Mol Dis. 2020; 85102481
      • 1.
        Uncertain benefit of HCQ and macrolides
      • 2.
        Cardiac (HCQ and macrolides) and renal (HCQ) toxicity
      		Avoid using HCQ/macrolide prophylaxis for AL amyloidosis, particularly those with cardiorenal involvement.
       SARS-Cov-2 vaccination
      • Jain A
      • Ramasamy K
      Potential 'significance' of monoclonal gammopathy of 'undetermined significance' during COVID-19 pandemic.
      Blood Cells Mol Dis. 2020; 85102481
      ,
      • Avivi I
      • Luttwak E
      • Saiag E
      • et al.
      BNT162b2 mRNA COVID-19 vaccine booster induces seroconversion in patients with B-cell non-Hodgkin lymphoma who failed to respond to two prior vaccine doses.
      Br J Haematol. 2022; 196: 1329-1333
      		Rituximab causes prolonged B-cell depletion lasting 6-12 months after the last doseRepeat SARS-CoV-2 vaccination at least 6-months after the last Rituximab dose
      Booster vaccination (mRNA vaccines) could augment antibody response following the second dose in patients with hematological malignancies
      • Avivi I
      • Luttwak E
      • Saiag E
      • et al.
      BNT162b2 mRNA COVID-19 vaccine booster induces seroconversion in patients with B-cell non-Hodgkin lymphoma who failed to respond to two prior vaccine doses.
      Br J Haematol. 2022; 196: 1329-1333
      		Consider booster vaccination for patients with AL amyloidosis who have completed the 2-dose schedule.
       Nephrological considerations
      • Jain A
      • Ramasamy K
      Potential 'significance' of monoclonal gammopathy of 'undetermined significance' during COVID-19 pandemic.
      Blood Cells Mol Dis. 2020; 85102481
      		Maintain COVID appropriate behaviour in the dialysis units
      • 1.
        Stagger patients requiring dialysis
      • 2.
        Consider peritoneal dialysis after nephrology consultation
       Diagnostic considerations
      • Jain A
      • Ramasamy K
      Potential 'significance' of monoclonal gammopathy of 'undetermined significance' during COVID-19 pandemic.
      Blood Cells Mol Dis. 2020; 85102481
      		Avoid organ biopsies for the diagnosis of AL amyloidosisConsider biopsy from alternate sites (abdominal fat pad)
      Therapeutic measures
       Treatment modifications
      • Jain A
      • Ramasamy K
      Potential 'significance' of monoclonal gammopathy of 'undetermined significance' during COVID-19 pandemic.
      Blood Cells Mol Dis. 2020; 85102481
      		CyBorD
      • 1.
        Reduce dexamethasone dose from 40 mg/week to 20 mg/week
      • 2.
        Use renal-modified dose of cyclophosphamide
      DARA-based regimensConsider 90-minute IV infusion following an uneventful first infusion, particularly in countries where SC formulation is not available
      HSCT and renal transplant cause prolonged immunosuppressionDefer both autologous HSCT and renal transplant for patients with AL amyloidosis, if feasible.
      B-NHL associated AL amyloidosis
      • 1.
        Purine analogues cause prolonged lymphodepletion.
      • 2.
        Rituximab can cause prolonged B-cell lymphopenia.
      • 3.
        IV Rituximab infusions needs hospitalisation
      • 1.
        Consider alkylator-based rituximab combinations
      • 2.
        Consider 2-monthly infusions instead of 3-monthly infusions during maintenance. $$$
      • 3.
        Consider SC rituximab
      Management of AL amyloidosis in patients infected with COVID-19
       Therapeutic measures
      • Jain A
      • Ramasamy K
      Potential 'significance' of monoclonal gammopathy of 'undetermined significance' during COVID-19 pandemic.
      Blood Cells Mol Dis. 2020; 85102481
      		Chemoimmunotherapy is potentially immunosuppressive
      • 1.
        Withhold the treatment of AL amyloidosis after the detection of COVID-19
      • 2.
        Resume treatment once COVID-19 is cured.
       General measures
      • Jain A
      • Ramasamy K
      Potential 'significance' of monoclonal gammopathy of 'undetermined significance' during COVID-19 pandemic.
      Blood Cells Mol Dis. 2020; 85102481
      		COVID-19 could cause cardiorenal decompensation in AL amyloidosis patientsConsider meticulous supportive care
       Response assessment
      • Jain A
      • Haynes R
      • Kothari J
      • Khera A
      • Soares M
      • Ramasamy K
      Pathophysiology and management of monoclonal gammopathy of renal significance.
      Blood Adv. 2019; 3: 2409-2423
      ,
      • Jain A
      • Ramasamy K
      Potential 'significance' of monoclonal gammopathy of 'undetermined significance' during COVID-19 pandemic.
      Blood Cells Mol Dis. 2020; 85102481
      • 1.
        COVID-19 infection could cause elevation of free kappa and lambda light chains
        • Jain A
        • Haynes R
        • Kothari J
        • Khera A
        • Soares M
        • Ramasamy K
        Pathophysiology and management of monoclonal gammopathy of renal significance.
        Blood Adv. 2019; 3: 2409-2423
      • 2.
        COVID-19 could cause renal impairment and elevation of cardiac biomarkers
      		Re-evaluate for hematological and organ response after COVID-19 is cured
      Management of COVID-19 in patients with AL amyloidosis
       Anti-COVID medications
      • Jain A
      • Ramasamy K
      Potential 'significance' of monoclonal gammopathy of 'undetermined significance' during COVID-19 pandemic.
      Blood Cells Mol Dis. 2020; 85102481
      ,
      • Kalil AC
      • Patterson TF
      • Mehta AK
      • et al.
      Baricitinib plus remdesivir for hospitalized adults with Covid-19.
      N Engl J Med. 2021; 384: 795-807
      ,
      • Jayk Bernal A
      • Gomes da Silva MM
      • Musungaie DB
      • et al.
      Molnupiravir for oral treatment of Covid-19 in non-hospitalized patients.
      N Engl J Med. 2022; 386: 509-520
      • 1.
        Remdesivir - cardiac and renal toxicity
      • 2.
        Baricitinib - renal toxicity
        • Kalil AC
        • Patterson TF
        • Mehta AK
        • et al.
        Baricitinib plus remdesivir for hospitalized adults with Covid-19.
        N Engl J Med. 2021; 384: 795-807
      • 3.
        Molnupiravir - no cardiorenal toxicities
        • Jayk Bernal A
        • Gomes da Silva MM
        • Musungaie DB
        • et al.
        Molnupiravir for oral treatment of Covid-19 in non-hospitalized patients.
        N Engl J Med. 2022; 386: 509-520
      • 4.
        Tocilizumab - may cause cardiac decompensation
      • 1.
        Cautious use in patients with cardiorenal amyloidosis
      • 2.
        Cautious use in patients with renal amyloidosis
      • 3.
        Consider using as per local approvals
      • 4.
        Cautious use in patients with cardiac amyloidosis
       Hemostatic considerations
      • Jain A
      • Ramasamy K
      Potential 'significance' of monoclonal gammopathy of 'undetermined significance' during COVID-19 pandemic.
      Blood Cells Mol Dis. 2020; 85102481
      • 1.
        Patients with AL amyloidosis have an inherent bleeding tendency
      • 2.
        Renal excretion of LMWH
      • 3.
        Reduced efficacy of heparin due to low AT
      • 1.
        Judicious use of anti-coagulation
      • 2.
        Anti-Xa-based LMWH dosing
      • 3.
        Consider use of dabigatran or argatroban
      AL = light chain; AT = antithrombin III; COVID-19 = Coronavirus disease 2019; CyBorD = cyclophosphamide, bortezomib, dexamethasone; DARA = daratumumab; HCQ = hydroxychloroquine; HSCT = hematopoietic stem cell transplant; IV = intravenous; LMWH = low-molecular-weight heparin; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SC = subcutaneous.

      References

        • Crees ZD
        • Stockerl-Goldstein K
        COVID-19 and light chain amyloidosis, adding insult to injury [online ahead of print].
        Am J Med. 2022 January 23; https://doi.org/10.1016/j.amjmed.2022.01.005
        View in Article
        • Jain A
        • Haynes R
        • Kothari J
        • Khera A
        • Soares M
        • Ramasamy K
        Pathophysiology and management of monoclonal gammopathy of renal significance.
        Blood Adv. 2019; 3: 2409-2423
        View in Article
        • Jain A
        • Ramasamy K
        Potential 'significance' of monoclonal gammopathy of 'undetermined significance' during COVID-19 pandemic.
        Blood Cells Mol Dis. 2020; 85102481
        View in Article
        • Avivi I
        • Luttwak E
        • Saiag E
        • et al.
        BNT162b2 mRNA COVID-19 vaccine booster induces seroconversion in patients with B-cell non-Hodgkin lymphoma who failed to respond to two prior vaccine doses.
        Br J Haematol. 2022; 196: 1329-1333
        View in Article
        • Kalil AC
        • Patterson TF
        • Mehta AK
        • et al.
        Baricitinib plus remdesivir for hospitalized adults with Covid-19.
        N Engl J Med. 2021; 384: 795-807
        View in Article
        • Jayk Bernal A
        • Gomes da Silva MM
        • Musungaie DB
        • et al.
        Molnupiravir for oral treatment of Covid-19 in non-hospitalized patients.
        N Engl J Med. 2022; 386: 509-520
        View in Article

      Article Info

      Footnotes

      Funding: None.

      Conflicts of Interest: None.

      Authorship: The sole author is responsible for all content.

      Identification

      DOI: https://doi.org/10.1016/j.amjmed.2022.02.011

      Copyright

      © 2022 Elsevier Inc. All rights reserved.

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