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Asymptomatic coronavirus disease followed by symptomatic reinfection in a patient with monoclonal gammopathy of undetermined significance: A case report

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Coronavirus disease (COVID-19) pandemic has been present for over a year and has been seen to behave unpredictably in different people especially those with other underlying health conditions. Monoclonal Gammopathy of Undetermined Significance (MGUS) is a rare condition that can alter immune responses. There are few case reports of COVID in people with MGUS and most of these are in elderly people often with associated comorbidities. The mutual impact of COVID and MGUS in younger people (<50 years) has been far less explored, and therefore, this case report would add to such data. Although there is no conclusive evidence to suggest that MGUS increases predisposition or significantly impacts the clinical course and outcomes of COVID-19, it can have some bearing on serological assessment in both COVID infected or vaccinated individuals.
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Online First Indian J Case Reports 1
Case Report
Asymptomatic coronavirus disease followed by symptomatic reinfection in a
patient with monoclonal gammopathy of undetermined significance: A case
report
Varsha Narayanan
From Consultant, Department of Family Medicine and Holistic Health, Dr. Varsha’s Health Solutions, Andheri West, Mumbai, Maharashtra, India
Coronavirus disease (COVID-19) has been present and
spreading globally for more than a year and has affected over
100 million people across more than 100 countries with over
2 million deaths (average mortality rate of 2–3%) [1]. It is a flu-like
illness seen to cause more severity, hospitalization, complications,
and mortality in the elderly and people with comorbidities. COVID
has been showing the second wave in many countries including
India, where the second wave is being seen from March 2021.
Monoclonal Gammopathy of Undetermined Significance (MGUS)
is considered a plasma cell dyscrasia with the presence of the M
protein (myeloma protein or monoclonal immunoglobulin), an
abnormal antibody usually discovered during laboratory tests [2].
The level of this antibody is lower (≤3 g/dl) in MGUS with
no end-organ damage, as compared to multiple myeloma, and
it rarely presents any symptoms or health problems. Population
prevalence of MGUS is around 2–3% in those aged 50 years or
more but <1% below 50 years, and ≤0.3% below 40 years of
age [3]. However, since MGUS can lead to multiple myeloma
in about 1% a year, annual follow-up, and health check-up is
recommended, with close monitoring of high-risk cases [4].
There is still very little evidence or medical insight available on
the mutual effects of COVID in people with MGUS.
CASE REPORT
A 45-year-old female corporate executive was diagnosed with
MGUS during a routine detailed pre-employment medical
check-up. Serum protein electrophoresis showed M band in gamma
region quantitated at 6.2% (0.42g/dl) (Fig. 1a); however, further
markers evaluated for high-risk MGUS were in the normal range
or negative (Fig. 1b). The rest of all the blood tests were normal.
The patient was already diagnosed with Grade 1 hypertension 3
years back and controlled on telmisartan 40 mg once daily. She
was advised yearly health check-ups and follow-up.
Three months later, the patient underwent nasal swab real-
time reverse transcriptase polymerase chain reaction (RT-PCR)
for COVID as a routine pre-travel procedure and requirement for
flying. While her first RT-PCR was negative on initiating travel,
the second done on her return from a 10-day official tour of 2–3
cities, was positive with a cycle threshold (Ct) of 32, suggesting
low viral load and transmissibility [5]. She had no symptoms of
COVID or any other infections or illness. She was kept under
isolation and observation with 4 hourly temperature and pulse
oximetry monitoring, and further evaluated with blood tests
(Table 1).
She was started on multi-vitamin supplements including B
complex, C, and D, with zinc. COVID RT-PCR was repeated on
the 5th day and was found to be negative. The patient remained
ABSTRACT
Coronavirus disease (COVID-19) pandemic has been present for over a year and has been seen to behave unpredictably in different
people especially those with other underlying health conditions. Monoclonal Gammopathy of Undetermined Significance (MGUS) is
a rare condition that can alter immune responses. There are few case reports of COVID in people with MGUS and most of these are in
elderly people often with associated comorbidities. The mutual impact of COVID and MGUS in younger people (<50 years) has been
far less explored, and therefore, this case report would add to such data. Although there is no conclusive evidence to suggest that MGUS
increases predisposition or significantly impacts the clinical course and outcomes of COVID-19, it can have some bearing on serological
assessment in both COVID infected or vaccinated individuals.
Key words: Antibodies, Asymptomatic, Coronavirus disease, Monoclonal Gammopathy of undetermined significance, Real-time
reverse transcriptase polymerase chain reaction
Access this article online
Received - 01 April 2021
Initial Review - 16 April 2021
Accepted - 24 April 2021
Quick Response code
DOI: ***
Correspondence to: Varsha Narayanan, 1305 Montreal, Shastri Nagar, Andheri
West, Mumbai - 400 053, Maharashtra, India. E-mail: info@drvarsha.com
© 2021 Creative Commons Attribution-NonCommercial 4.0 International
License (CC BY-NC-ND 4.0).
Online First Indian J Case Reports 2
Narayanan Asymptomatic COVID in MGUS
asymptomatic, with normal temperature and oxygen saturation
(maintained above 95%) through the 5 days of observation. At the
end of 2 weeks, the patient had remained without any symptoms
and felt perfectly well. Anti-severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) total antibodies (by serum ECLIA)
were estimated, which was non-reactive at 0.0668 (laboratory
cutoff for reactive ≥1).
Forty days later after testing negative with RT-PCR, she
developed fever (101°F), sore throat, and dry cough. She
was immediately asked to isolate herself and RT-PCR was
performed which was positive with a cycle threshold (Ct) of
18, suggesting high viral load and transmissibility [5]. She was
kept under isolation and observation with 4 hourly temperature
and pulse oximetry monitoring, and further evaluated with
blood tests (Table 1). She was given favipiravir, paracetamol,
and symptomatic treatment for cough along with continuing the
multi-vitamin and zinc supplements. Fever was absent by the 3rd
day, and full recovery of symptoms seen with oxygen saturation
maintained above 95%. Antiviral treatment was given for 10
days, and the 14-day isolation period was completed.
She was advised to follow all the protocols for COVID
and vaccine administration after 8 weeks as well as an annual
health check-up for MGUS. Anti- SARS-CoV-2 total antibodies
(by serum ECLIA) were estimated, which was reactive at 2.06
(laboratory cutoff for reactive ≥1).
DISCUSSION
MGUS is usually an incidental diagnosis, as in this case. Although
the rate of progression to myeloma is only 1% per year, this rate
does not decrease with time; therefore, lifelong regular follow-up
is recommended. Markers of high-risk MGUS in terms of
progression to multiple myeloma such as M protein of at least 1.5
g/dl, monoclonal immunoglobulin other than IgG, and an abnormal
Figure 1: Diagnostic tests for Monoclonal Gammopathy of Unknown Significance. (a) Serum protein electrophoresis; (b) Other markers
a
b
Online First Indian J Case Reports 3
Narayanan Asymptomatic COVID in MGUS
serum free light-chain ratio (kappa:lambda light chains) were absent
in this case. There is some evidence to suggest that since MGUS
may be associated with hypogammaglobulinemia (in almost 25%)
and sub-optimal immunity, hypercoagulability, and a greater
propensity for end-organ damage, this could possibly increase the
susceptibility, severity, and mortality (up to 15%) of COVID-19
in the elderly population who are already in a higher COVID risk
group due to age and associated comorbidities [6]. However, there
is a lack of evidence to suggest the same in younger populations
below 50 years. Whether MGUS actually significantly impacts the
clinical course of COVID needs study in a larger population, and
as of now, there is no such data to suggest that MGUS may impart
either additional risks, or affect patient outcomes in COVID [7].
In this case, the patient was initially asymptomatic, showed a
negative RT-PCR test within 5 days and no antibody response at
2 weeks, followed by developing symptoms and testing positive
around 6 weeks later. The patient raised the question whether the
first RT-PCR test when asymptomatic was a false-positive result.
Factors such as sample contamination, technological variations
in a number of contiguous nucleic acid bases, second separation
technique, amplification errors with short probes, and data-
software errors can yield a false positive [8]. Such false positives
have seen to be rare at the rate of 0.8–4%. It is to be noted that
in this case, the first positive RT-PCR was from a standardized
accredited laboratory, displaying the cycle threshold, while the
patient had significant exposure to COVID due to travel, visiting
multiple venues, and mingling with several people, therefore a
false positive RT-PCR seemed unlikely.
The reason to explain achieving early RT-PCR negative status
after the initial infection could be that asymptomatic persons with
low viral load show early viral clearance [9,10]. A study showed
a median viral clearance time of 7 days in asymptomatic versus
16.5 days in mild-moderate symptomatic patients [11]. The virus-
specific antibody response in asymptomatic COVID positive
people has been seen to be significantly lower than the symptomatic
group. A study showed more than 80% of asymptomatic individuals
had a reduction in neutralizing antibody levels, during the early
convalescent phase with 40% (vs. 13% in the symptomatic group)
becoming seronegative for IgG in the early convalescent phase,
suggesting that asymptomatic individuals had a weaker immune
response to SARS-CoV-2 infection [12]. The reduction in IgG
and neutralizing antibody levels in the early convalescent phase
might have implications for immunization strategy and serological
surveys, as well as for the risk of early re-infection, as seen in this
case [13]. It is also to be noted that the re-infection occurred during
an aggressive resurge of COVID in India and also the identification
of double mutant more infective variants [14].
MGUS is known to be a condition that can decrease antibody
response to infections and vaccination [6,15]. People with
MGUS may have impaired anti-viral antibody response and
a lower SARS-CoV-2 specific IgG as compared to the general
population [6]. However, the clinical and real-world significance
and impact of this on COVID susceptibility, clinical course, and
immunological response are still not ascertained, and the same
would be more significant in the elderly with waning immunity.
All infected people especially with initial low viral load should be
made aware of possible re-infection anytime and therefore always
follow standard precautions. As per recommendations, all people
with MGUS should be vaccinated against COVID-19; however,
more research on post-vaccination seroconversion and SARS-
CoV-2-specific IgG titer antibody titers is required in this group,
along with the effect of age and other comorbidities.
CONCLUSION
Asymptomatic people testing positive with RT-PCR for COVID
can show low viral load and transmissibility, along with early viral
clearance, followed by re-infection within a short time span. The
presence of MGUS in younger people <50 years may not affect
the clinical course or outcomes in COVID. However, a person
with MGUS with asymptomatic or mild COVID may show
the absence of COVID-specific antibodies and immunological
response on serological testing. These points can be kept in mind
during patient counseling, serological surveys, and population
vaccination drives. Research and studies in a larger number of
people with MGUS, especially younger patients with high-risk
MGUS, are required to add further medical insights on how this
condition impacts risk, course, and outcomes in COVID, along
with a response to vaccination.
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Table 1: Real-time reverse transcriptase polymerase chain reaction
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Test Asymptomatic
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Symptomatic
reinfection
Real-time reverse transcriptase
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Ferritin 7.1 ng/ml 10.7 ng/ml
Lactate dehydrogenase 142 U/l 156 U/l1
Interleukin 6 2.2 pg/ml 9.3 pg/ml
Anti-severe acute respiratory
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Non-reactive Reactive
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Funding: None; Conflicts of Interest: None Stated.
How to cite this article: Narayanan V. Asymptomatic coronavirus
disease followed by symptomatic reinfection in a patient with
monoclonal gammopathy of undetermined significance: A case
report. Indian J Case Reports. 2021; May 09 [Epub ahead of print].
ResearchGate has not been able to resolve any citations for this publication.
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