key: cord-1037258-50fvkd4a
authors: Zaidi, Syed Ziauddin Ahmed; Zaidi, Fatima Zia; AlShehry, Nawal; Zaidi, Abdul Rehman Zia; Zaidi, Saleha Zia; Abdullah, Syed Maaz
title: Aging and therapy‐related hypogammaglobulinemia causing pneumonia: An overlooked curable entity in the chaotic COVID‐19 pandemic
date: 2020-07-28
journal: J Med Virol
DOI: 10.1002/jmv.26318
sha: 57d486ad8837548721ba443296a3396b37093349
doc_id: 1037258
cord_uid: 50fvkd4a

nan

Aging and therapy-related hypogammaglobulinemia causing pneumonia: An overlooked curable entity in the chaotic COVID-19 pandemic

To the Editor, There are multiple reports that the chaos caused by the coronavirus disease-2019 (COVID-19) pandemic has diverted our attention and priorities from some other equally or more important diseases. 1 Amidst the COVID-19 pandemic, in any respiratory illness, causing pneumonia or sinusitis, the first thing that predominates our thought process is the possibility of COVID-19. It becomes more obvious in the emergency department setting, as triage staff is provided with preset COVID-19 pathways and scores defining patient's categorization in most hospitals. For example, with a known diagnosis of cancer who presents with cough and fever with pneumonia, a high probability of COVID-19 is assigned and nasopharyngeal swabs (NPS) are sent on priority for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR). If one test comes negative, still another swab is sent with a high probability of COVID-19 in the mind. Due to discomfort, some patients may not be cooperative enough to obtain a proper NPS. 2 Moreover, obtaining NPS is a potentially risky procedure for healthcare workers. Hence, despite using proper personal protective equipment, an anxious proceduralist may lack the zeal to perform a high-quality swab. Although gargle lavage has been proposed as a safer and possibly more yielding procedure 2 but is not adopted yet in practice. All these factors further delay ruling out the possibility of COVID-19.

During such chaotic periods, we often neglect aging and therapyrelated hypogammaglobulinemia that could be causing pneumonia or sinopulmonary infection in the elderly population. SARS-CoV-2 may cause infection by chance in such a patient. Despite the fact that we do not have any specific COVID-19 therapies, all efforts and time are diverted toward COVID-19 management protocols, instead of a multidirectional approach to include a more curable hypogammaglobulinemiarelated bacterial pneumonia. Another factor that may lead to such an erroneous path in hematological cancer patients, and some autoimmune disorders, is the presence of lymphopenia due to therapies targeting lymphocytes (specifically B cells), as lymphopenia is an established highrisk factor for the development of severe COVID-19 disease in the elderly. 3 Hypogammaglobulinemia can be observed at extremes of age. 4, 5 Hypogammaglobulinemia is reported in the elderly population. 5 Buckley and Dorsey 5 reported a gradual decrease in Immunoglobulin G (IgG) and IgM concentrations with aging, IgG decreased considerably from third through the sixth decade. This deficiency is also discovered in blood banks in ∼4% of cases of ABO blood group discrepancy reflected by missing or weak ABO isoantibodies during reverse grouping. 6 Hypogammaglobulinemia in adults may be seen in hematological malignancies, particularly chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). 7 In CLL, 27%-52% of patients have hypogammaglobulinemia 8 and transiently in 38.5% of patients after anti-CD20 therapy. 9 Other causes include immunosuppressive therapies, viral infections, 10 radiation, and immunoglobulin deficiency related to enteropathies, renal, or cutaneous loss. 7 When a cause cannot be identified, the condition is labeled as a primary immune deficiency; most frequently a diagnosis of common variable immunodeficiency is made. 10 Secondary hypogammaglobulinemia is estimated to be 30 times more frequent than primary hypogammaglobulinemia. 7 Blot et al 11 compared between severe and mild hypogammaglobulinemia (gamma globulin levels <5 g/L, and ≥5 to <6.4 g/L, respectively) in a retrospective observational study that included 389 adult patients (age range 52-82 years). They reported a similar etiology and infection risk in both groups. The main etiologies included hematological malignancies. 11 The incidence of hypogammaglobulinemia-related infections in both groups was ∼22/100/year (P = .17), where 78% of these were pulmonary infections (P = .12). 11 No etiology of hypogammaglobulinemia was found in 27.76% of the patients. 11 We speculate it could be attributed to a primary deficiency or simply be a reflection of aging.

Streptococcus pneumoniae or Haemophilus influenzae infections in more than one-third of the patients. 12 Valdamalai et al 13 reported a 38% prevalence of hypogammaglobinemia in patients with communityacquired pneumonia. 13 Interestingly, Cowan et al 14 in a retrospective cohort of invasive pneumococcal disease patients, found that 72.2% of those with an underlying hematological malignancy (CLL, lymphoma, and MM) had hypogammaglobulinemia. Timely diagnosis before the

The untold toll-the pandemic's effects on patients without Covid-19

Gargle lavage as a safe and sensitive alternative to swab samples to diagnose COVID-19: a case report in Japan

The diagnostic and predictive role of NLR, d-NLR and PLR in COVID-19 patients

Transient hypogammaglobulinemia of infancy

The effect of aging on human serum immunoglobulin concentrations

Resolving ABO discrepancies by serological workup-an analysis of few cases

The expanding field of secondary antibody deficiency: causes, diagnosis, and management

Immunoglobulin G subclass deficiency and infection risk in 150 patients with chronic lymphocytic leukemia

Incidence of hypogammaglobulinemia in patients receiving rituximab and the use of intravenous immunoglobulin for recurrent infections

Evaluating and managing hypogammaglobulinemia

Should mild hypogammaglobulinemia be managed as severe hypogammaglobulinemia? A study of 389 patients with secondary hypogammaglobulinemia

Immunoglobulin deficiency in patients with Streptococcus pneumoniae or Haemophilus influenzae invasive infections

Screening for humoral immunodeficiency in patients with community-acquired pneumonia

Prevalence of hypogammaglobulinemia in adult invasive pneumococcal disease

Current clinical practice and challenges in the management of secondary immunodeficiency in hematological malignancies