Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences · 2025
Расследование результатов и лечение длинных коронавирусных заболеваний 2019 года у пациентов с множественным склерозом, обработанных ритуксимаб: тематическое исследование.
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Shirani Kiana, Khorvash Farzin, Karamshahi Alireza, Maghamimehr Asieh
Аннотация
Множественный склероз (MS) — хроническое аутоиммунное заболевание, затрагивающее центральную нервную систему, характеризующееся разрушением миелинской ножки нервов. Пациенты MS, которые лечились ритуксимабом, иммунодепрессивным препаратом, страдают от снижения уровня иммуноглобулина, что повышает их риск различных инфекций, включая коронавирусную болезнь 2019 года (COVID-19). Во время пандемии COVID-19 у многих из этих пациентов появились долгосрочные симптомы после инфицирования. Эти хронические симптомы привели к значительным осложнениям, а в некоторых случаях к росту смертности. В ходе этого исследования мы изучили длинные симптомы COVID-19 у пациентов, проходящих курс лечения ритуксимаба, и последствия внутривенной иммуноглобулиновой терапии (ИВИГ) для смягчения хронических симптомов. Результаты показали, что долгосрочные симптомы пациентов были приняты во внимание при лечении ИВГ, что привело к значительному улучшению симптомов дыхания, лихорадки, иммунных параметров и снижению уровня белка, реагирующего на С. В этом исследовании подчеркивается важность целенаправленного управления долголетним COVID-19 у лиц с иммунокомпромиссной популяцией и высказывается мысль о том, что для лечения пациентов с иммунной недостаточностью по линии COVID-19 требуются конкретные терапевтические подходы.
Оригинал публикации
Investigating outcomes and treatment of long coronavirus disease 2019 in patients with multiple sclerosis treated with rituximab: A case series study.
Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system, characterized by the destruction of the myelin sheath of nerves. MS patients treated with rituximab, an immunosuppressive drug, experience reduced immunoglobulin levels, which increases their risk of various infections, including coronavirus disease 2019 (COVID-19). During the COVID-19 pandemic, many of these patients developed long-term symptoms following infection. These chronic symptoms have led to significant complications and, in some cases, increased mortality. In this case series study, we investigated long COVID-19 symptoms in MS patients treated with rituximab and the effects of intravenous immunoglobulin (IVIG) therapy in alleviating chronic symptoms. The results demonstrated that the patients' long-term symptoms responded to IVIG treatment, with significant improvements in respiratory symptoms, fever, immune parameters, and a reduction in C-reactive protein levels. This study highlights the importance of targeted management of long COVID-19 in immunocompromised populations and suggests that COVID-19 patients with immune deficiencies require specific therapeutic approaches.
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INTRODUCTION
The coronavirus disease 2019 (COVID-19) has been recognized as a public health emergency of international concern.[ 1 ] From the early stages of the pandemic, it was suggested that immunocompromised patients, including those receiving immunosuppressive therapies, might face a higher risk of contracting the virus and experiencing more severe and prolonged forms of the disease.[ 2 ]
Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system characterized by the destruction of myelin and axons, leading to progressive disability.[ 3 ] Common treatments for MS include immunosuppressive agents such as rituximab.[ 4 ] Rituximab, a monoclonal anti-CD20 antibody, depletes B-cells and is an effective therapy for controlling MS progression.[ 5 ] However, long-term use of this drug is associated with reduced gamma globulin (immunoglobulin G [IgG]) levels and an increased risk of viral infections, including SARS-CoV-2.[ 6 , 7 ]
Managing MS patients during the COVID-19 pandemic has been challenging due to the use of immunomodulatory therapies. Previous studies indicate that MS patients treated with anti-CD20 agents like rituximab not only face a higher risk of contracting COVID-19 but also experience prolonged disease courses and more severe complications.[ 8 ] Consequently, some clinical guidelines recommend cautious administration of anti-CD20 drugs in MS patients, as these therapies increase the risk of COVID-19 by 3- to 4-fold.[ 9 ] Cohort studies have further shown that MS patients on rituximab have higher hospitalization rates compared to the general population, though no significant increase in mortality has been observed.[ 10 ]
Recent studies suggest that reduced IgG levels (due to rituximab use) may exacerbate long-term COVID-19 symptoms, such as fatigue, dyspnea, and cognitive impairment, in MS patients.[ 11 ] In this context, intravenous immunoglobulin (IVIG) therapy has emerged as a potential strategy to compensate for IgG deficiency and reduce systemic inflammation. By elevating IgG levels and enhancing antiviral immune responses, IVIG may alleviate respiratory and neurological symptoms.[ 12 ]
This case series study, conducted at Alzahra Hospital in Isfahan, included eight rituximab-treated MS patients who developed long-term symptoms after COVID-19 infection. The study aimed to investigate long COVID-19 and evaluate the efficacy of IVIG in managing prolonged COVID-19 symptoms in these patients, particularly those who exhibited poor responses to standard therapies such as corticosteroids and remdesivir. Given that clinical symptoms, including frequent respiratory infections and general weakness, in patients receiving rituximab have shown a strong association with low IgG level,[ 13 ] and due to the lack of access to rapid assessment of IgG levels, we substituted clinical assessment for IVIG administration in our cases.
CASE REPORTS
Case 1
A 45-year-old woman with a 17-year history of MS had been on a therapeutic regimen of rituximab infusions every 6 months. She presented to Alzahra Hospital in Isfahan 25 days prior with fever, chills, dyspnea, arthralgia, and generalized weakness. The patient reported no comorbidities other than MS and denied tobacco, alcohol, or illicit drug use. Her last rituximab infusion was administered approximately 5 months earlier.
On admission, her vital signs were as follows: temperature 38.5°C, respiratory rate (RR) 30 breaths/min, oxygen saturation (SaO₂) 96% on room air, blood pressure (BP) 100/60 mmHg, and heart rate 97 beats/min. Physical examination revealed diminished breath sounds in the right lung. A SARS-CoV-2 polymerase chain reaction (PCR) test performed during her initial visit returned positive. Blood and biochemical tests were conducted [ Table 1 ].
Table 1 Complete laboratory examinations at the emergency department on the first visit and subsequent visits Lab First visit Next day of receiving IVIG Last visit Laboratory reference range White blood cells (K/μL) 6200 - - 4.0–10.8 Neutrophils (%) 68 - - 40–75 Lymphocytes (%) 22 - - 20–45 Hemoglobin (g/dL) 12 - - 12.3–15.5 Red blood cells (M/μL) 4.25 - - 4.1–5.1 Platelets 200,000 - - 150,000–440,000 Potassium (mmol/L) 4.7 - 4.5 3.60–5.00 Sodium (mmol/L) 143 - 140 135–150 BUN (mg/dL) 7 - - 7–18.6 Creatinine (mg/dL) 0.9 - - 0.7–1.3 Lactate dehydrogenase (U/L) 741 - - 100–480 Creatine phosphokinase (U/L) 40 - - 30–170 Alkaline phosphatase (U/L) 209 - - 100–240 Aspartate aminotransferase (U/L) 28 - - 15–59 Alanine aminotransferase (U/L) 22 - - 10–72 CRP (mg/L) 43 13 6 0.0–5.0 Arterial blood gas on air pH 7.50 - 7.35 pO 2 (mmHg) 82.1 - 92.6 pCO 2 (mmHg) 17.8 - 29.9 HCO 3 (mmol/L) 15.1 - 16.2 SaO 2 (%) 95 - 96.5 Urinalysis Negative - - pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
Complete laboratory examinations at the emergency department on the first visit and subsequent visits
pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
The patient was admitted to the infectious disease ward. A chest computed tomography (CT) scan demonstrated an atypical pneumonia pattern consistent with COVID-19 pneumonia. On day 1, she received remdesivir (200 mg loading dose followed by 100 mg daily for 5 days), intravenous dexamethasone (8 mg daily for 4 days), and empirical antibiotic therapy with levofloxacin, linezolid, and meropenem. Despite treatment, the patient remained febrile 24 h after admission. All laboratory findings, except for elevated C-reactive protein (CRP), were within normal ranges, and arterial blood gas analysis showed no hypoxemia [ Table 1 ].
On day 2 of hospitalization, IVIG was added to her treatment regimen (with a single dose of 0.4 g/kg). Her fever resolved within 24 h of IVIG administration, and she showed clinical improvement in respiratory symptoms. By day 27, all clinical symptoms, including fever, had subsided, and CRP levels normalized. The patient was discharged 4 days after IVIG initiation following confirmation of sustained clinical recovery.
Case 2
A 54-year-old man with a 5-year history of MS had been on a therapeutic regimen of rituximab infusions every 6 months. He presented to Alzahra Hospital in Isfahan 14 days prior with fever, dyspnea, and cough. Prior to admission, he had received levofloxacin for 5 days with no clinical improvement. The patient reported no comorbidities other than MS and denied tobacco, alcohol, or illicit drug use. His last rituximab infusion was administered approximately 3 months earlier.
On admission, his vital signs were as follows: temperature 37.9°C, RR 28 breaths/min, SaO₂ 93% on room air, BP 114/92 mmHg, and heart rate 89 beats/min. Physical examination revealed diminished breath sounds in both lungs. A SARS-CoV-2 PCR test performed during his initial visit returned positive. Blood and biochemical tests were conducted [ Table 2 ].
Table 2 Complete laboratory examinations at the emergency department on the first visit and subsequent visits Lab First visit Next day of receiving IVIG Last visit Laboratory reference range White blood cells (K/μL) 5400 6800 4700 4400–11,000 Neutrophils (%) 93.2 85 82 50–70 Lymphocytes (%) 5.8 7 10.8 20–40 Hemoglobin (g/dL) 11.8 11.7 12.1 14–17.5 Red blood cells (M/μL) 4 3.86 4.1 4.1–5.1 Platelets 274,000 263,000 230,000 150,000–440,000 Potassium (mmol/L) 4.5 - 4.5 3.60–5.00 Sodium (mmol/L) 137 - 140 135–150 BUN (mg/dL) 12 - - 7–18.6 Creatinine (mg/dL) 0.8 - - 0.7–1.3 Lactate dehydrogenase (U/L) 497 - - 100–480 Creatine phosphokinase (U/L) 227 - - 30–170 Alkaline phosphatase (U/L) 192 - - 100–240 Aspartate aminotransferase (U/L) 28 - - 15–59 Alanine aminotransferase (U/L) 20 - - 10–72 CRP (mg/L) 128 92 44 0.0–5.0 Arterial blood gas on air pH 7.37 - - pO 2 (mmHg) 91 - - pCO 2 (mmHg) 26.2 - - HCO 3 (mmol/L) 18 - - SaO 2 (%) 93 - - Urinalysis Negative - - pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
Complete laboratory examinations at the emergency department on the first visit and subsequent visits
pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
The patient was admitted to the infectious disease ward. A chest CT scan demonstrated atypical pneumonia patterns consistent with COVID-19 pneumonia, involving the entire right lower lobe and part of the left lower lobe. On day 2, he received remdesivir (200 mg loading dose followed by 100 mg daily for 5 days), intravenous dexamethasone (8 mg for 1 day), methylprednisolone (50 mg for 1 day), and empirical antibiotic therapy with levofloxacin and ampicillin. Despite 72 h of treatment, the patient remained febrile. All laboratory findings, except for elevated CRP, were within normal ranges, and arterial blood gas analysis showed no hypoxemia [ Table 2 ].
On day 4 of hospitalization, IVIG was added to his treatment regimen (with a single dose of 0.4 g/kg). His fever and dyspnea resolved within 24 h of IVIG administration, and he showed clinical improvement in respiratory symptoms. By day 16, all clinical symptoms, including fever and dyspnea, had subsided, and CRP levels normalized. The patient was discharged 5 days after IVIG initiation following confirmation of sustained clinical recovery.
Case 3
A 48-year-old male with a 16-year history of MS had been on a therapeutic regimen of rituximab infusions every 6 months. He presented to Alzahra Hospital in Isfahan 50 days prior with fever and chills. The patient had two prior hospitalizations and received treatment with corticosteroids, gentamicin, co-amoxiclav, levofloxacin, and ceftazidime, which yielded no improvement. The patient reported a history of seizures in addition to MS and denied tobacco, alcohol, or illicit drug use. His last rituximab infusion was administered approximately 3 months earlier.
On admission, his vital signs were as follows: temperature 38°C, RR 18 breaths/min, SaO₂ 95% on room air, BP 110/70 mmHg, and heart rate 101 beats/min. Physical examination revealed crackles in both lungs. A SARS-CoV-2 PCR test performed during his initial visit returned positive. Blood and biochemical tests were conducted [ Table 3 ].
Table 3 Complete laboratory examinations at the emergency department on the first visit and subsequent visits Lab First visit Next day of receiving IVIG Laste visit Laboratory reference range White blood cells (K/μL) 7200 - - 4.0–10.8 Neutrophils (%) 75 - - 40–75 Lymphocytes (%) 13.5 - - 20–45 Hemoglobin (g/dL) 12.6 - - 14–17.5 Red blood cells (M/μL) 4.35 - - 4.1–5.1 Platelets 136,000 - - 150,000–440,000 Potassium (mmol/L) 4.4 - 4.5 3.60–5.00 Sodium (mmol/L) 138 - 138 135–150 BUN (mg/dL) 16 23 21 7–18.6 Creatinine (mg/dL) 0.9 1 0.8 0.7–1.3 Alkaline phosphatase (U/L) 183 - - 100–240 Aspartate aminotransferase (U/L) 15 - - 15–59 Alanine aminotransferase (U/L) 30 - - 10–72 CRP (mg/L) 49 34 10 0.0–5.0 Arterial blood gas on air pH 7.36 - - pO 2 (mmHg) 87 - - pCO 2 (mmHg) 36 - - HCO 3 (mmol/L) 22 - - SaO 2 (%) 95 - - Urinalysis Negative - - pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
Complete laboratory examinations at the emergency department on the first visit and subsequent visits
pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
The patient was admitted to the infectious disease ward. A chest CT scan demonstrated bilateral multilobar atypical pneumonia consistent with COVID-19 pneumonia. On day 1, he received remdesivir (200 mg loading dose followed by 100 mg daily for 5 days), intravenous dexamethasone (8 mg daily for 3 days), and prednisolone (25 mg daily for 3 days). Despite 48 h of treatment, the patient remained febrile. All laboratory findings, except for elevated CRP, were within normal ranges, and arterial blood gas analysis showed no hypoxemia [ Table 3 ].
On day 3 of hospitalization, IVIG was added to his treatment regimen (with a single dose of 0.4 g/kg). His fever resolved within 48 h of IVIG administration, and he showed clinical improvement in respiratory symptoms. By day 55, all clinical symptoms, including fever and chills, had subsided, and CRP levels normalized. The patient was discharged 4 days after IVIG initiation following confirmation of sustained clinical recovery.
Case 4
A 34-year-old woman with a 15-year history of MS had been on a therapeutic regimen of rituximab infusions every 6 months. She presented to Alzahra Hospital in Isfahan 15 days prior with fever, chills, dry cough, and headache. Prior to admission, she had received treatment with cefixime, azithromycin, clindamycin, levofloxacin, and ceftriaxone, which yielded no improvement. The patient reported no comorbidities other than MS and denied tobacco, alcohol, or illicit drug use. Her last rituximab infusion was administered approximately 6 months earlier.
On admission, her vital signs were as follows: temperature 37.8°C, RR 17 breaths/min, SaO₂ 96% on room air, BP 110/65 mmHg, and heart rate 88 beats/min. Physical examination revealed crackles in the right lung and the base of the left lung. A SARS-CoV-2 PCR test performed during her initial visit returned positive. Blood and biochemical tests were conducted [ Table 4 ].
Table 4 Complete laboratory examinations at the emergency department on the first visit and subsequent visits Lab First visit Next day of receiving IVIG Last visit Laboratory reference range White blood cells (K/μL) 5100 - - 4.0–10.8 Neutrophils (%) 92 - - 40–75 Lymphocytes (%) 6 - - 20–45 Hemoglobin (g/dL) 9 - - 12.3–15.5 Red blood cells (M/μL) 4.59 - - 4.1–5.1 Platelets 247,000 - - 150,000–440,000 Potassium (mmol/L) 4.7 4 4.1 3.60–5.00 Sodium (mmol/L) 143 145 139 135–150 BUN (mg/dL) 10 14 - 7–18.6 Creatinine (mg/dL) 1.1 1 - 0.7–1.3 Alkaline phosphatase (U/L) 119 - - 100–240 Aspartate aminotransferase (U/L) 27 - - 10–33 Alanine aminotransferase (U/L) 10 - - 10–33 CRP (mg/L) 79 58 28 0.0–5.0 Vein blood gas on air pH 7.37 - - pO 2 (mmHg) 41 - - pCO 2 (mmHg) 22.6 - - HCO 3 (mmol/L) 41 - - SaO 2 (%) 74.4 - - Urinalysis Negative - - pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
Complete laboratory examinations at the emergency department on the first visit and subsequent visits
pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
The patient was admitted to the infectious disease ward. A chest CT scan demonstrated atypical multilobar pneumonia in the right lung and the left upper lobe, consistent with COVID-19 pneumonia. On day 1, she received remdesivir (200 mg loading dose followed by 100 mg daily for 5 days), intravenous dexamethasone (8 mg daily for 3 days), and prednisolone (25 mg daily for 7 days). Despite 24 h of treatment, the patient remained febrile. All laboratory findings, except for elevated CRP, were within normal ranges, and arterial blood gas analysis showed no hypoxemia [ Table 4 ].
On day 2 of hospitalization, IVIG was added to her treatment regimen (with a single dose of 0.4 g/kg). Her fever resolved within 24 h of IVIG administration, and she showed clinical improvement in respiratory symptoms. By day 17, all clinical symptoms, including fever and chills, had subsided, and CRP levels normalized. The patient was discharged 3 days after IVIG initiation following confirmation of sustained clinical recovery.
Case 5
A 58-year-old male with a 12-year history of MS had been on a therapeutic regimen of rituximab infusions every 6 months. He presented to Alzahra Hospital in Isfahan 3 months prior with severe cough and dyspnea. Prior to admission, he had received treatment with linezolid and levofloxacin for 7 days with no clinical improvement. The patient reported no comorbidities other than MS and denied tobacco, alcohol, or illicit drug use. His last rituximab infusion was administered approximately 3 months earlier.
On admission, his vital signs were as follows: temperature 40.1°C, RR 24 breaths/min, SaO₂ 91% on room air, BP 110/60 mmHg, and heart rate 75 beats/min. Physical examination revealed diffuse wheezing in both lungs. A SARS-CoV-2 PCR test performed during his initial visit returned positive. Blood and biochemical tests were conducted [ Table 5 ].
Table 5 Complete laboratory examinations at the emergency department on the first visit and subsequent visits Lab First visit Next day of receiving IVIG Last visit Laboratory reference range White blood cells (K/μL) 7100 - - 4400–11,000 Neutrophils (%) 80 - - 50–70 Lymphocytes (%) 11.3 - - 20–40 Hemoglobin (g/dL) 13.4 - - 14–17.5 Red blood cells (M/μL) 4.54 - - 4.1–5.1 Platelets 310,000 - - 150,000–440,000 Potassium (mmol/L) 4.4 - 4.3 3.60–5.00 Sodium (mmol/L) 141 - 135 135–150 BUN (mg/dL) 13 12 - 7–18.6 Creatinine (mg/dL) 1.1 1 - 0.7–1.3 Lactate dehydrogenase (U/L) 549 - - 100–480 Aspartate aminotransferase (U/L) 32 - - 15–59 Alanine aminotransferase (U/L) 65 - - 10–72 CRP (mg/L) 78 30 22 0.0–5.0 Vein blood gas on air pH 7.36 - - pO 2 (mmHg) 44 - - pCO 2 (mmHg) 40.4 - - HCO 3 (mmol/L) 22.5 - - SaO 2 (%) 77.9 - - Urinalysis Negative - - pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
Complete laboratory examinations at the emergency department on the first visit and subsequent visits
pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
The patient was admitted to the infectious disease ward. A chest CT scan demonstrated atypical pneumonia consistent with COVID-19 pneumonia. On day 1, he received remdesivir (200 mg loading dose followed by 100 mg daily for 5 days), intravenous dexamethasone (8 mg daily for 2 days), and methylprednisolone (5 mg daily for 5 days). Despite 4 days of treatment, the patient remained febrile. All laboratory findings, except for elevated CRP, were within normal ranges, and arterial blood gas analysis showed no hypoxemia [ Table 5 ].
On day 4 of hospitalization, IVIG was added to his treatment regimen (with a single dose of 0.4 g/kg). His dyspnea resolved within 24 h of IVIG administration, and he showed clinical improvement in respiratory symptoms. By day 95, all clinical symptoms, including dyspnea, had subsided, and CRP levels normalized. The patient was discharged 3 days after IVIG initiation, following confirmation of sustained clinical recovery.
Case 6
A 34-year-old woman with a 14-year history of MS had been on a therapeutic regimen of rituximab infusions every 6 months. She presented to Alzahra Hospital in Isfahan 60 days prior with fever, dry cough, and dyspnea. The patient reported no comorbidities other than MS and denied tobacco, alcohol, or illicit drug use. Her last rituximab infusion was administered approximately 4 months earlier.
On admission, her vital signs were as follows: temperature 39°C, RR 30 breaths/min, SaO₂ 72% on room air, BP 120/70 mmHg, and heart rate 121 beats/min. Physical examination revealed crackles in both lungs. A SARS-CoV-2 PCR test performed during her initial visit returned positive. Blood and biochemical tests were conducted [ Table 6 ].
Table 6 Complete laboratory examinations at the emergency department on the first visit and subsequent visits Lab First visit Next day of receiving IVIG Last visit Laboratory reference range White blood cells (K/μL) 12,500 - - 4.0–10.8 Neutrophils (%) 93 - - 40–75 Lymphocytes (%) 6 - - 20–45 Hemoglobin (g/dL) 13.2 - - 12.3–15.5 Red blood cells (M/μL) 4.34 - - 4.1–5.1 Platelets 183,000 - - 150,000–440,000 Potassium (mmol/L) 5.5 4.3 - 3.60–5.00 Sodium (mmol/L) 143 137 - 135–150 BUN (mg/dL) 7 14 - 7–18.6 Creatinine (mg/dL) 0.8 1 - 0.7–1.3 Lactate dehydrogenase (U/L) 904 - - 100–480 Creatine phosphokinase (U/L) 58 - - 30–180 Alkaline phosphatase (U/L) 175 - - 100–240 Aspartate aminotransferase (U/L) 55 - - 10–33 Alanine aminotransferase (U/L) 32 - - 10–33 CRP (mg/L) 176 38 10 0.0–5.0 Arterial blood gas on air pH 7.41 - - pO 2 (mmHg) 55.5 - - pCO 2 (mmHg) 42 -- - HCO 3 (mmol/L) 26.3 - - SaO 2 (%) 89 - - Urinalysis Negative - - pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
Complete laboratory examinations at the emergency department on the first visit and subsequent visits
pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
The patient was admitted to the infectious disease ward. A chest CT scan demonstrated bilateral viral bronchopneumonia. On day 1, she received remdesivir (200 mg loading dose followed by 100 mg daily for 5 days), intravenous dexamethasone (8 mg daily for 10 days), and empirical antibiotic therapy with linezolid and piperacillin-tazobactam for 6 days. Despite 6 days of treatment, the patient remained febrile. All laboratory findings, except for elevated CRP, were within normal ranges [ Table 6 ].
On day 6 of hospitalization, IVIG was added to her treatment regimen (with a single dose of 0.4 g/kg). Her fever resolved within 24 h of IVIG administration, and she showed clinical improvement in respiratory symptoms. By day 67, all clinical symptoms, including fever and dyspnea, had subsided, and CRP levels normalized. The patient was discharged 4 days after IVIG initiation following confirmation of sustained clinical recovery.
Case 7
A 62-year-old woman with a 13-year history of MS had been on a therapeutic regimen of rituximab infusions every 6 months. She presented to Alzahra Hospital in Isfahan 14 days prior with fever, dyspnea, and dry cough. Prior to admission, she had received treatment with remdesivir, dexamethasone, and prednisolone for COVID-19, with no clinical improvement. The patient reported no comorbidities other than MS and denied tobacco, alcohol, or illicit drug use. Her last rituximab infusion was administered approximately 6 months earlier.
On admission, her vital signs were as follows: temperature 39.5°C, RR 16 breaths/min, SaO₂ 84% on room air, BP 115/80 mmHg, and heart rate 86 beats/min. Physical examination revealed diffuse wheezing in both lungs. A SARS-CoV-2 PCR test performed during her initial visit returned positive. Blood and biochemical tests were conducted [ Table 7 ].
Table 7 Complete laboratory examinations at the emergency department on the first visit and subsequent visits Lab First visit Next day of receiving IVIG Last visit Laboratory reference range White blood cells (K/μL) 9100 - 4500 4400–11,000 Neutrophils (%) 84.8 - 76 50–70 Lymphocytes (%) 5.6 - 9.7 20–40 Hemoglobin (g/dL) 12.8 - 12.2 12.3–15.5 Red blood cells (M/μL) 5 - 4.5 4.1–5.1 Platelets 203,000 - 199,000 150,000–440,000 Potassium (mmol/L) 4.9 3.5 4.2 3.60–5.00 Sodium (mmol/L) 131 139 141 135–150 BUN (mg/dL) 16 38 - 7–18.6 Creatinine (mg/dL) 0.9 1.2 - 0.7–1.3 Lactate dehydrogenase (U/L) 549 - - 100–480 Aspartate aminotransferase (U/L) 17 - - 15–59 Alanine aminotransferase (U/L) 14 - - 10–72 Alkaline phosphatase (U/L) 208 100–240 CRP (mg/L) 60.3 27 3 0.0–5.0 Vein blood gas on air pH 7.34 - - pO 2 (mmHg) 29.4 - - pCO 2 (mmHg) 55 - - HCO 3 (mmol/L) 32.7 - - SaO 2 (%) 56.7 - - Urinalysis Negative - - pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
Complete laboratory examinations at the emergency department on the first visit and subsequent visits
pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
The patient was admitted to the infectious disease ward. A chest CT scan demonstrated atypical pneumonia consistent with COVID-19 pneumonia, involving over 50% of both lungs. On day 5, she received remdesivir (200 mg loading dose followed by 100 mg daily for 5 days), oral prednisolone (50 mg daily for 10 days), and empirical antibiotic therapy with meropenem and levofloxacin for 14 days starting on day 1. Despite 12 days of treatment, the patient remained febrile. All laboratory findings, except for elevated CRP, were within normal ranges [ Table 7 ].
On day 13 of hospitalization, IVIG was added to her treatment regimen (with a single dose of 0.4 g/kg). Her dyspnea resolved within 3 days of IVIG administration, and she showed clinical improvement in respiratory symptoms. SaO₂ improved to 94% on room air. By day 26, all clinical symptoms, including dyspnea, had subsided, and CRP levels normalized. The patient was discharged 4 days after IVIG initiation following confirmation of sustained clinical recovery.
Case 8
A 44-year-old male with a 13-year history of MS had been on a therapeutic regimen of rituximab infusions every 6 months. He presented to Alzahra Hospital in Isfahan 7 days prior with a high-grade fever (41°C) and cough. The patient reported no comorbidities other than MS and denied tobacco, alcohol, or illicit drug use. His last rituximab infusion was administered approximately 5 months earlier.
On admission, his vital signs were as follows: temperature 39.5°C, RR 18 breaths/min, SaO₂ 95% on room air, BP 140/80 mmHg, and heart rate 100 beats/min. Physical examination revealed no pathological findings on lung auscultation. A SARS-CoV-2 PCR test performed during his initial visit returned positive. Blood and biochemical tests were conducted [ Table 8 ].
Table 8 Complete laboratory examinations at the emergency department on the first visit and subsequent visits Lab First visit Next day of receiving IVIG Last visit Laboratory reference range White blood cells (K/μL) 2300 - - 4400−11,000 Neutrophils (%) 79 - - 50−70 Lymphocytes (%) 8.5 - - 20−40 Hemoglobin (g/dL) 14 - - 14−17.5 Red blood cells (M/μL) 4.59 - - 4.1−5.1 Platelets 143,000 - - 150,000−440,000 Potassium (mmol/L) 3.5 3.7 4.4 3.60−5.00 Sodium (mmol/L) 142 137 141 135−150 BUN (mg/dL) 8 - 6 7−18.6 Creatinine (mg/dL) 1 - 1.1 0.7−1.3 Lactate dehydrogenase (U/L) 327 - - 100−480 Creatine phosphokinase (U/L) 124 - - 30−170 Alkaline phosphatase (U/L) 153 - - 100−240 Aspartate aminotransferase (U/L) 31 - - 15−59 Alanine aminotransferase (U/L) 49 - - 10−72 CRP (mg/L) 84 40 15 0.0−5.0 Arterial blood gas on air pH 7.40 - - pO 2 (mmHg) 61.3 - - pCO 2 (mmHg) 33.2 - - HCO 3 (mmol/L) 20.2 - - SaO 2 (%) 91 - - Urinalysis Negative - - pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
Complete laboratory examinations at the emergency department on the first visit and subsequent visits
pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
The patient was admitted to the infectious disease ward. A chest CT scan demonstrated atypical pneumonia consistent with COVID-19 pneumonia. On day 1, he received remdesivir (200 mg loading dose followed by 100 mg daily for 5 days), intravenous dexamethasone (8 mg daily for 3 days), and empirical antibiotic therapy with levofloxacin and ampicillin. Despite 48 h of treatment, the patient remained febrile. All laboratory findings and elevated CRP are shown in Table 8 .
On day 3 of hospitalization, IVIG was added to his treatment regimen (with a single dose of 0.4 g/kg). His fever resolved within 24 h of IVIG administration, and he showed clinical improvement. By day 10, all clinical symptoms, including fever, had subsided, and CRP levels normalized. The patient was discharged 3 days after IVIG initiation following confirmation of sustained clinical recovery.
In Table 9 , a comparison between eight patients was made based on symptoms, paraclinical findings, and medication use.
Table 9 Compare 8 cases Case number Symptoms Duration symptoms First CRP Last CRP Medication 1 Fever, chills, dyspnea, arthralgia, generalized weakness 27 days 43 6 Remdesivir, intravenous dexamethasone, levofloxacin, linezolid, meropenem, IVIG 2 Fever, dyspnea, cough 16 days 128 44 Remdesivir, intravenous dexamethasone, methylprednisolone, levofloxacin ampicillin, IVIG 3 fever, chills 55 days 49 10 Remdesivir, intravenous dexamethasone, and prednisolone, IVIG 4 Fever, chills, dry cough, headache 17 days 79 28 Remdesivir, intravenous dexamethasone, prednisolone, IVIG 5 Severe cough, dyspnea 95 days 78 22 Remdesivir, intravenous dexamethasone, methylprednisolone, IVIG 6 Fever, dry cough, dyspnea 67 days 176 10 Remdesivir, intravenous dexamethasone, linezolid, piperacillin-tazobactam, IVIG 7 Fever, dyspnea, dry cough 26 days 60.3 3 Remdesivir, oral prednisolone, meropenem, levofloxacin, IVIG 8 High-grade fever, cough 10 days 84 15 Remdesivir, intravenous dexamethasone, levofloxacin, ampicillin, IVIG CRP=C-reactive protein; IVIG=Intravenous immunoglobulin
Compare 8 cases
CRP=C-reactive protein; IVIG=Intravenous immunoglobulin
Written informed consent has been taken from all patients, and the ethical code for this research is: IR.MUI.MED.REC.1403.436.
DISCUSSION
This study demonstrated that IVIG therapy significantly alleviates long COVID-19 symptoms in MS patients treated with rituximab. Elevated IgG levels and reduced inflammatory markers, such as CRP, indicate humoral immune reconstitution and diminished systemic inflammation. These findings align with the work of Thompson et al .,[ 12 ] who reported marked IgG improvement following IVIG.
While corticosteroids (e.g., dexamethasone) and remdesivir are standard therapies for severe COVID-19,[ 8 ] their efficacy is limited in patients with profound immune deficiencies, such as those on rituximab.[ 7 , 14 ] A cohort study of 150 MS patients revealed that remdesivir induced clinical improvement in only 22% of cases,[ 12 ] likely due to suppressed humoral immunity and impaired neutralizing antibody production.[ 15 ] Johnson et al .[ 9 ] found that rituximab-treated MS patients face a threefold higher risk of developing long COVID-19 compared to the general population. IVIG, however, reduced respiratory symptoms by 40% in these patients and doubled recovery rates compared to remdesivir in immunocompromised cohorts.[ 16 ] Martinez et al .[ 10 ] further confirmed IVIG’s effectiveness in mitigating chronic COVID-19 symptoms such as fatigue and dyspnea.
Rituximab disrupts IgG production by suppressing B cells.[ 4 , 9 ] In contrast, IVIG enhances antiviral immunity by replenishing polyclonal antibodies, curbing SARS-CoV-2 replication,[ 17 , 18 ] and attenuating pulmonary and neurological inflammation through inhibition of pro-inflammatory cytokines such as interleukin-6 and tumor necrosis factor-alpha.[ 15 , 19 ] IVIG also modulates macrophage overactivation by binding to Fcγ receptors.[ 20 ]
Multiple studies validate IVIG’s role in ameliorating long COVID-19 symptoms and restoring humoral immunity. For instance, Gelfand[ 11 ] demonstrated that IVIG elevates IgG levels and reduces systemic inflammation. In addition, IVIG promotes immune balance by expanding regulatory T-cells, thereby preventing cytokine storms.[ 19 ] Similar studies corroborate IVIG’s capacity to enhance antiviral responses and alleviate long COVID-19 manifestations.[ 18 , 21 ]
Clinical evidence suggests IVIG reduces long COVID-19-related hospitalization risks by 40% in MS patients.[ 18 , 22 , 23 ] Notably, in MS patients with IgG levels below 400 mg/dL, IVIG shortened symptom duration from 12 weeks to 4 weeks.[ 24 ]
CONCLUSION
IVIG holds significant potential for managing long COVID-19 in rituximab-treated MS patients. By improving immune parameters and reducing inflammation, IVIG could serve as an adjunctive strategy in therapeutic protocols for this population. However, further research is essential to determine optimal dosing, evaluate long-term effects, and analyze cost-effectiveness.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Conflicts of interest
There are no conflicts of interest.
Funding Statement
Nil.
REFERENCES
The coronavirus disease 2019 (COVID-19) has been recognized as a public health emergency of international concern.[ 1 ] From the early stages of the pandemic, it was suggested that immunocompromised patients, including those receiving immunosuppressive therapies, might face a higher risk of contracting the virus and experiencing more severe and prolonged forms of the disease.[ 2 ]
Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system characterized by the destruction of myelin and axons, leading to progressive disability.[ 3 ] Common treatments for MS include immunosuppressive agents such as rituximab.[ 4 ] Rituximab, a monoclonal anti-CD20 antibody, depletes B-cells and is an effective therapy for controlling MS progression.[ 5 ] However, long-term use of this drug is associated with reduced gamma globulin (immunoglobulin G [IgG]) levels and an increased risk of viral infections, including SARS-CoV-2.[ 6 , 7 ]
Managing MS patients during the COVID-19 pandemic has been challenging due to the use of immunomodulatory therapies. Previous studies indicate that MS patients treated with anti-CD20 agents like rituximab not only face a higher risk of contracting COVID-19 but also experience prolonged disease courses and more severe complications.[ 8 ] Consequently, some clinical guidelines recommend cautious administration of anti-CD20 drugs in MS patients, as these therapies increase the risk of COVID-19 by 3- to 4-fold.[ 9 ] Cohort studies have further shown that MS patients on rituximab have higher hospitalization rates compared to the general population, though no significant increase in mortality has been observed.[ 10 ]
Recent studies suggest that reduced IgG levels (due to rituximab use) may exacerbate long-term COVID-19 symptoms, such as fatigue, dyspnea, and cognitive impairment, in MS patients.[ 11 ] In this context, intravenous immunoglobulin (IVIG) therapy has emerged as a potential strategy to compensate for IgG deficiency and reduce systemic inflammation. By elevating IgG levels and enhancing antiviral immune responses, IVIG may alleviate respiratory and neurological symptoms.[ 12 ]
This case series study, conducted at Alzahra Hospital in Isfahan, included eight rituximab-treated MS patients who developed long-term symptoms after COVID-19 infection. The study aimed to investigate long COVID-19 and evaluate the efficacy of IVIG in managing prolonged COVID-19 symptoms in these patients, particularly those who exhibited poor responses to standard therapies such as corticosteroids and remdesivir. Given that clinical symptoms, including frequent respiratory infections and general weakness, in patients receiving rituximab have shown a strong association with low IgG level,[ 13 ] and due to the lack of access to rapid assessment of IgG levels, we substituted clinical assessment for IVIG administration in our cases.
CASE REPORTS
Case 1
A 45-year-old woman with a 17-year history of MS had been on a therapeutic regimen of rituximab infusions every 6 months. She presented to Alzahra Hospital in Isfahan 25 days prior with fever, chills, dyspnea, arthralgia, and generalized weakness. The patient reported no comorbidities other than MS and denied tobacco, alcohol, or illicit drug use. Her last rituximab infusion was administered approximately 5 months earlier.
On admission, her vital signs were as follows: temperature 38.5°C, respiratory rate (RR) 30 breaths/min, oxygen saturation (SaO₂) 96% on room air, blood pressure (BP) 100/60 mmHg, and heart rate 97 beats/min. Physical examination revealed diminished breath sounds in the right lung. A SARS-CoV-2 polymerase chain reaction (PCR) test performed during her initial visit returned positive. Blood and biochemical tests were conducted [ Table 1 ].
Table 1 Complete laboratory examinations at the emergency department on the first visit and subsequent visits Lab First visit Next day of receiving IVIG Last visit Laboratory reference range White blood cells (K/μL) 6200 - - 4.0–10.8 Neutrophils (%) 68 - - 40–75 Lymphocytes (%) 22 - - 20–45 Hemoglobin (g/dL) 12 - - 12.3–15.5 Red blood cells (M/μL) 4.25 - - 4.1–5.1 Platelets 200,000 - - 150,000–440,000 Potassium (mmol/L) 4.7 - 4.5 3.60–5.00 Sodium (mmol/L) 143 - 140 135–150 BUN (mg/dL) 7 - - 7–18.6 Creatinine (mg/dL) 0.9 - - 0.7–1.3 Lactate dehydrogenase (U/L) 741 - - 100–480 Creatine phosphokinase (U/L) 40 - - 30–170 Alkaline phosphatase (U/L) 209 - - 100–240 Aspartate aminotransferase (U/L) 28 - - 15–59 Alanine aminotransferase (U/L) 22 - - 10–72 CRP (mg/L) 43 13 6 0.0–5.0 Arterial blood gas on air pH 7.50 - 7.35 pO 2 (mmHg) 82.1 - 92.6 pCO 2 (mmHg) 17.8 - 29.9 HCO 3 (mmol/L) 15.1 - 16.2 SaO 2 (%) 95 - 96.5 Urinalysis Negative - - pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
Complete laboratory examinations at the emergency department on the first visit and subsequent visits
pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
The patient was admitted to the infectious disease ward. A chest computed tomography (CT) scan demonstrated an atypical pneumonia pattern consistent with COVID-19 pneumonia. On day 1, she received remdesivir (200 mg loading dose followed by 100 mg daily for 5 days), intravenous dexamethasone (8 mg daily for 4 days), and empirical antibiotic therapy with levofloxacin, linezolid, and meropenem. Despite treatment, the patient remained febrile 24 h after admission. All laboratory findings, except for elevated C-reactive protein (CRP), were within normal ranges, and arterial blood gas analysis showed no hypoxemia [ Table 1 ].
On day 2 of hospitalization, IVIG was added to her treatment regimen (with a single dose of 0.4 g/kg). Her fever resolved within 24 h of IVIG administration, and she showed clinical improvement in respiratory symptoms. By day 27, all clinical symptoms, including fever, had subsided, and CRP levels normalized. The patient was discharged 4 days after IVIG initiation following confirmation of sustained clinical recovery.
Case 2
A 54-year-old man with a 5-year history of MS had been on a therapeutic regimen of rituximab infusions every 6 months. He presented to Alzahra Hospital in Isfahan 14 days prior with fever, dyspnea, and cough. Prior to admission, he had received levofloxacin for 5 days with no clinical improvement. The patient reported no comorbidities other than MS and denied tobacco, alcohol, or illicit drug use. His last rituximab infusion was administered approximately 3 months earlier.
On admission, his vital signs were as follows: temperature 37.9°C, RR 28 breaths/min, SaO₂ 93% on room air, BP 114/92 mmHg, and heart rate 89 beats/min. Physical examination revealed diminished breath sounds in both lungs. A SARS-CoV-2 PCR test performed during his initial visit returned positive. Blood and biochemical tests were conducted [ Table 2 ].
Table 2 Complete laboratory examinations at the emergency department on the first visit and subsequent visits Lab First visit Next day of receiving IVIG Last visit Laboratory reference range White blood cells (K/μL) 5400 6800 4700 4400–11,000 Neutrophils (%) 93.2 85 82 50–70 Lymphocytes (%) 5.8 7 10.8 20–40 Hemoglobin (g/dL) 11.8 11.7 12.1 14–17.5 Red blood cells (M/μL) 4 3.86 4.1 4.1–5.1 Platelets 274,000 263,000 230,000 150,000–440,000 Potassium (mmol/L) 4.5 - 4.5 3.60–5.00 Sodium (mmol/L) 137 - 140 135–150 BUN (mg/dL) 12 - - 7–18.6 Creatinine (mg/dL) 0.8 - - 0.7–1.3 Lactate dehydrogenase (U/L) 497 - - 100–480 Creatine phosphokinase (U/L) 227 - - 30–170 Alkaline phosphatase (U/L) 192 - - 100–240 Aspartate aminotransferase (U/L) 28 - - 15–59 Alanine aminotransferase (U/L) 20 - - 10–72 CRP (mg/L) 128 92 44 0.0–5.0 Arterial blood gas on air pH 7.37 - - pO 2 (mmHg) 91 - - pCO 2 (mmHg) 26.2 - - HCO 3 (mmol/L) 18 - - SaO 2 (%) 93 - - Urinalysis Negative - - pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
Complete laboratory examinations at the emergency department on the first visit and subsequent visits
pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
The patient was admitted to the infectious disease ward. A chest CT scan demonstrated atypical pneumonia patterns consistent with COVID-19 pneumonia, involving the entire right lower lobe and part of the left lower lobe. On day 2, he received remdesivir (200 mg loading dose followed by 100 mg daily for 5 days), intravenous dexamethasone (8 mg for 1 day), methylprednisolone (50 mg for 1 day), and empirical antibiotic therapy with levofloxacin and ampicillin. Despite 72 h of treatment, the patient remained febrile. All laboratory findings, except for elevated CRP, were within normal ranges, and arterial blood gas analysis showed no hypoxemia [ Table 2 ].
On day 4 of hospitalization, IVIG was added to his treatment regimen (with a single dose of 0.4 g/kg). His fever and dyspnea resolved within 24 h of IVIG administration, and he showed clinical improvement in respiratory symptoms. By day 16, all clinical symptoms, including fever and dyspnea, had subsided, and CRP levels normalized. The patient was discharged 5 days after IVIG initiation following confirmation of sustained clinical recovery.
Case 3
A 48-year-old male with a 16-year history of MS had been on a therapeutic regimen of rituximab infusions every 6 months. He presented to Alzahra Hospital in Isfahan 50 days prior with fever and chills. The patient had two prior hospitalizations and received treatment with corticosteroids, gentamicin, co-amoxiclav, levofloxacin, and ceftazidime, which yielded no improvement. The patient reported a history of seizures in addition to MS and denied tobacco, alcohol, or illicit drug use. His last rituximab infusion was administered approximately 3 months earlier.
On admission, his vital signs were as follows: temperature 38°C, RR 18 breaths/min, SaO₂ 95% on room air, BP 110/70 mmHg, and heart rate 101 beats/min. Physical examination revealed crackles in both lungs. A SARS-CoV-2 PCR test performed during his initial visit returned positive. Blood and biochemical tests were conducted [ Table 3 ].
Table 3 Complete laboratory examinations at the emergency department on the first visit and subsequent visits Lab First visit Next day of receiving IVIG Laste visit Laboratory reference range White blood cells (K/μL) 7200 - - 4.0–10.8 Neutrophils (%) 75 - - 40–75 Lymphocytes (%) 13.5 - - 20–45 Hemoglobin (g/dL) 12.6 - - 14–17.5 Red blood cells (M/μL) 4.35 - - 4.1–5.1 Platelets 136,000 - - 150,000–440,000 Potassium (mmol/L) 4.4 - 4.5 3.60–5.00 Sodium (mmol/L) 138 - 138 135–150 BUN (mg/dL) 16 23 21 7–18.6 Creatinine (mg/dL) 0.9 1 0.8 0.7–1.3 Alkaline phosphatase (U/L) 183 - - 100–240 Aspartate aminotransferase (U/L) 15 - - 15–59 Alanine aminotransferase (U/L) 30 - - 10–72 CRP (mg/L) 49 34 10 0.0–5.0 Arterial blood gas on air pH 7.36 - - pO 2 (mmHg) 87 - - pCO 2 (mmHg) 36 - - HCO 3 (mmol/L) 22 - - SaO 2 (%) 95 - - Urinalysis Negative - - pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
Complete laboratory examinations at the emergency department on the first visit and subsequent visits
pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
The patient was admitted to the infectious disease ward. A chest CT scan demonstrated bilateral multilobar atypical pneumonia consistent with COVID-19 pneumonia. On day 1, he received remdesivir (200 mg loading dose followed by 100 mg daily for 5 days), intravenous dexamethasone (8 mg daily for 3 days), and prednisolone (25 mg daily for 3 days). Despite 48 h of treatment, the patient remained febrile. All laboratory findings, except for elevated CRP, were within normal ranges, and arterial blood gas analysis showed no hypoxemia [ Table 3 ].
On day 3 of hospitalization, IVIG was added to his treatment regimen (with a single dose of 0.4 g/kg). His fever resolved within 48 h of IVIG administration, and he showed clinical improvement in respiratory symptoms. By day 55, all clinical symptoms, including fever and chills, had subsided, and CRP levels normalized. The patient was discharged 4 days after IVIG initiation following confirmation of sustained clinical recovery.
Case 4
A 34-year-old woman with a 15-year history of MS had been on a therapeutic regimen of rituximab infusions every 6 months. She presented to Alzahra Hospital in Isfahan 15 days prior with fever, chills, dry cough, and headache. Prior to admission, she had received treatment with cefixime, azithromycin, clindamycin, levofloxacin, and ceftriaxone, which yielded no improvement. The patient reported no comorbidities other than MS and denied tobacco, alcohol, or illicit drug use. Her last rituximab infusion was administered approximately 6 months earlier.
On admission, her vital signs were as follows: temperature 37.8°C, RR 17 breaths/min, SaO₂ 96% on room air, BP 110/65 mmHg, and heart rate 88 beats/min. Physical examination revealed crackles in the right lung and the base of the left lung. A SARS-CoV-2 PCR test performed during her initial visit returned positive. Blood and biochemical tests were conducted [ Table 4 ].
Table 4 Complete laboratory examinations at the emergency department on the first visit and subsequent visits Lab First visit Next day of receiving IVIG Last visit Laboratory reference range White blood cells (K/μL) 5100 - - 4.0–10.8 Neutrophils (%) 92 - - 40–75 Lymphocytes (%) 6 - - 20–45 Hemoglobin (g/dL) 9 - - 12.3–15.5 Red blood cells (M/μL) 4.59 - - 4.1–5.1 Platelets 247,000 - - 150,000–440,000 Potassium (mmol/L) 4.7 4 4.1 3.60–5.00 Sodium (mmol/L) 143 145 139 135–150 BUN (mg/dL) 10 14 - 7–18.6 Creatinine (mg/dL) 1.1 1 - 0.7–1.3 Alkaline phosphatase (U/L) 119 - - 100–240 Aspartate aminotransferase (U/L) 27 - - 10–33 Alanine aminotransferase (U/L) 10 - - 10–33 CRP (mg/L) 79 58 28 0.0–5.0 Vein blood gas on air pH 7.37 - - pO 2 (mmHg) 41 - - pCO 2 (mmHg) 22.6 - - HCO 3 (mmol/L) 41 - - SaO 2 (%) 74.4 - - Urinalysis Negative - - pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
Complete laboratory examinations at the emergency department on the first visit and subsequent visits
pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
The patient was admitted to the infectious disease ward. A chest CT scan demonstrated atypical multilobar pneumonia in the right lung and the left upper lobe, consistent with COVID-19 pneumonia. On day 1, she received remdesivir (200 mg loading dose followed by 100 mg daily for 5 days), intravenous dexamethasone (8 mg daily for 3 days), and prednisolone (25 mg daily for 7 days). Despite 24 h of treatment, the patient remained febrile. All laboratory findings, except for elevated CRP, were within normal ranges, and arterial blood gas analysis showed no hypoxemia [ Table 4 ].
On day 2 of hospitalization, IVIG was added to her treatment regimen (with a single dose of 0.4 g/kg). Her fever resolved within 24 h of IVIG administration, and she showed clinical improvement in respiratory symptoms. By day 17, all clinical symptoms, including fever and chills, had subsided, and CRP levels normalized. The patient was discharged 3 days after IVIG initiation following confirmation of sustained clinical recovery.
Case 5
A 58-year-old male with a 12-year history of MS had been on a therapeutic regimen of rituximab infusions every 6 months. He presented to Alzahra Hospital in Isfahan 3 months prior with severe cough and dyspnea. Prior to admission, he had received treatment with linezolid and levofloxacin for 7 days with no clinical improvement. The patient reported no comorbidities other than MS and denied tobacco, alcohol, or illicit drug use. His last rituximab infusion was administered approximately 3 months earlier.
On admission, his vital signs were as follows: temperature 40.1°C, RR 24 breaths/min, SaO₂ 91% on room air, BP 110/60 mmHg, and heart rate 75 beats/min. Physical examination revealed diffuse wheezing in both lungs. A SARS-CoV-2 PCR test performed during his initial visit returned positive. Blood and biochemical tests were conducted [ Table 5 ].
Table 5 Complete laboratory examinations at the emergency department on the first visit and subsequent visits Lab First visit Next day of receiving IVIG Last visit Laboratory reference range White blood cells (K/μL) 7100 - - 4400–11,000 Neutrophils (%) 80 - - 50–70 Lymphocytes (%) 11.3 - - 20–40 Hemoglobin (g/dL) 13.4 - - 14–17.5 Red blood cells (M/μL) 4.54 - - 4.1–5.1 Platelets 310,000 - - 150,000–440,000 Potassium (mmol/L) 4.4 - 4.3 3.60–5.00 Sodium (mmol/L) 141 - 135 135–150 BUN (mg/dL) 13 12 - 7–18.6 Creatinine (mg/dL) 1.1 1 - 0.7–1.3 Lactate dehydrogenase (U/L) 549 - - 100–480 Aspartate aminotransferase (U/L) 32 - - 15–59 Alanine aminotransferase (U/L) 65 - - 10–72 CRP (mg/L) 78 30 22 0.0–5.0 Vein blood gas on air pH 7.36 - - pO 2 (mmHg) 44 - - pCO 2 (mmHg) 40.4 - - HCO 3 (mmol/L) 22.5 - - SaO 2 (%) 77.9 - - Urinalysis Negative - - pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
Complete laboratory examinations at the emergency department on the first visit and subsequent visits
pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
The patient was admitted to the infectious disease ward. A chest CT scan demonstrated atypical pneumonia consistent with COVID-19 pneumonia. On day 1, he received remdesivir (200 mg loading dose followed by 100 mg daily for 5 days), intravenous dexamethasone (8 mg daily for 2 days), and methylprednisolone (5 mg daily for 5 days). Despite 4 days of treatment, the patient remained febrile. All laboratory findings, except for elevated CRP, were within normal ranges, and arterial blood gas analysis showed no hypoxemia [ Table 5 ].
On day 4 of hospitalization, IVIG was added to his treatment regimen (with a single dose of 0.4 g/kg). His dyspnea resolved within 24 h of IVIG administration, and he showed clinical improvement in respiratory symptoms. By day 95, all clinical symptoms, including dyspnea, had subsided, and CRP levels normalized. The patient was discharged 3 days after IVIG initiation, following confirmation of sustained clinical recovery.
Case 6
A 34-year-old woman with a 14-year history of MS had been on a therapeutic regimen of rituximab infusions every 6 months. She presented to Alzahra Hospital in Isfahan 60 days prior with fever, dry cough, and dyspnea. The patient reported no comorbidities other than MS and denied tobacco, alcohol, or illicit drug use. Her last rituximab infusion was administered approximately 4 months earlier.
On admission, her vital signs were as follows: temperature 39°C, RR 30 breaths/min, SaO₂ 72% on room air, BP 120/70 mmHg, and heart rate 121 beats/min. Physical examination revealed crackles in both lungs. A SARS-CoV-2 PCR test performed during her initial visit returned positive. Blood and biochemical tests were conducted [ Table 6 ].
Table 6 Complete laboratory examinations at the emergency department on the first visit and subsequent visits Lab First visit Next day of receiving IVIG Last visit Laboratory reference range White blood cells (K/μL) 12,500 - - 4.0–10.8 Neutrophils (%) 93 - - 40–75 Lymphocytes (%) 6 - - 20–45 Hemoglobin (g/dL) 13.2 - - 12.3–15.5 Red blood cells (M/μL) 4.34 - - 4.1–5.1 Platelets 183,000 - - 150,000–440,000 Potassium (mmol/L) 5.5 4.3 - 3.60–5.00 Sodium (mmol/L) 143 137 - 135–150 BUN (mg/dL) 7 14 - 7–18.6 Creatinine (mg/dL) 0.8 1 - 0.7–1.3 Lactate dehydrogenase (U/L) 904 - - 100–480 Creatine phosphokinase (U/L) 58 - - 30–180 Alkaline phosphatase (U/L) 175 - - 100–240 Aspartate aminotransferase (U/L) 55 - - 10–33 Alanine aminotransferase (U/L) 32 - - 10–33 CRP (mg/L) 176 38 10 0.0–5.0 Arterial blood gas on air pH 7.41 - - pO 2 (mmHg) 55.5 - - pCO 2 (mmHg) 42 -- - HCO 3 (mmol/L) 26.3 - - SaO 2 (%) 89 - - Urinalysis Negative - - pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
Complete laboratory examinations at the emergency department on the first visit and subsequent visits
pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
The patient was admitted to the infectious disease ward. A chest CT scan demonstrated bilateral viral bronchopneumonia. On day 1, she received remdesivir (200 mg loading dose followed by 100 mg daily for 5 days), intravenous dexamethasone (8 mg daily for 10 days), and empirical antibiotic therapy with linezolid and piperacillin-tazobactam for 6 days. Despite 6 days of treatment, the patient remained febrile. All laboratory findings, except for elevated CRP, were within normal ranges [ Table 6 ].
On day 6 of hospitalization, IVIG was added to her treatment regimen (with a single dose of 0.4 g/kg). Her fever resolved within 24 h of IVIG administration, and she showed clinical improvement in respiratory symptoms. By day 67, all clinical symptoms, including fever and dyspnea, had subsided, and CRP levels normalized. The patient was discharged 4 days after IVIG initiation following confirmation of sustained clinical recovery.
Case 7
A 62-year-old woman with a 13-year history of MS had been on a therapeutic regimen of rituximab infusions every 6 months. She presented to Alzahra Hospital in Isfahan 14 days prior with fever, dyspnea, and dry cough. Prior to admission, she had received treatment with remdesivir, dexamethasone, and prednisolone for COVID-19, with no clinical improvement. The patient reported no comorbidities other than MS and denied tobacco, alcohol, or illicit drug use. Her last rituximab infusion was administered approximately 6 months earlier.
On admission, her vital signs were as follows: temperature 39.5°C, RR 16 breaths/min, SaO₂ 84% on room air, BP 115/80 mmHg, and heart rate 86 beats/min. Physical examination revealed diffuse wheezing in both lungs. A SARS-CoV-2 PCR test performed during her initial visit returned positive. Blood and biochemical tests were conducted [ Table 7 ].
Table 7 Complete laboratory examinations at the emergency department on the first visit and subsequent visits Lab First visit Next day of receiving IVIG Last visit Laboratory reference range White blood cells (K/μL) 9100 - 4500 4400–11,000 Neutrophils (%) 84.8 - 76 50–70 Lymphocytes (%) 5.6 - 9.7 20–40 Hemoglobin (g/dL) 12.8 - 12.2 12.3–15.5 Red blood cells (M/μL) 5 - 4.5 4.1–5.1 Platelets 203,000 - 199,000 150,000–440,000 Potassium (mmol/L) 4.9 3.5 4.2 3.60–5.00 Sodium (mmol/L) 131 139 141 135–150 BUN (mg/dL) 16 38 - 7–18.6 Creatinine (mg/dL) 0.9 1.2 - 0.7–1.3 Lactate dehydrogenase (U/L) 549 - - 100–480 Aspartate aminotransferase (U/L) 17 - - 15–59 Alanine aminotransferase (U/L) 14 - - 10–72 Alkaline phosphatase (U/L) 208 100–240 CRP (mg/L) 60.3 27 3 0.0–5.0 Vein blood gas on air pH 7.34 - - pO 2 (mmHg) 29.4 - - pCO 2 (mmHg) 55 - - HCO 3 (mmol/L) 32.7 - - SaO 2 (%) 56.7 - - Urinalysis Negative - - pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
Complete laboratory examinations at the emergency department on the first visit and subsequent visits
pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
The patient was admitted to the infectious disease ward. A chest CT scan demonstrated atypical pneumonia consistent with COVID-19 pneumonia, involving over 50% of both lungs. On day 5, she received remdesivir (200 mg loading dose followed by 100 mg daily for 5 days), oral prednisolone (50 mg daily for 10 days), and empirical antibiotic therapy with meropenem and levofloxacin for 14 days starting on day 1. Despite 12 days of treatment, the patient remained febrile. All laboratory findings, except for elevated CRP, were within normal ranges [ Table 7 ].
On day 13 of hospitalization, IVIG was added to her treatment regimen (with a single dose of 0.4 g/kg). Her dyspnea resolved within 3 days of IVIG administration, and she showed clinical improvement in respiratory symptoms. SaO₂ improved to 94% on room air. By day 26, all clinical symptoms, including dyspnea, had subsided, and CRP levels normalized. The patient was discharged 4 days after IVIG initiation following confirmation of sustained clinical recovery.
Case 8
A 44-year-old male with a 13-year history of MS had been on a therapeutic regimen of rituximab infusions every 6 months. He presented to Alzahra Hospital in Isfahan 7 days prior with a high-grade fever (41°C) and cough. The patient reported no comorbidities other than MS and denied tobacco, alcohol, or illicit drug use. His last rituximab infusion was administered approximately 5 months earlier.
On admission, his vital signs were as follows: temperature 39.5°C, RR 18 breaths/min, SaO₂ 95% on room air, BP 140/80 mmHg, and heart rate 100 beats/min. Physical examination revealed no pathological findings on lung auscultation. A SARS-CoV-2 PCR test performed during his initial visit returned positive. Blood and biochemical tests were conducted [ Table 8 ].
Table 8 Complete laboratory examinations at the emergency department on the first visit and subsequent visits Lab First visit Next day of receiving IVIG Last visit Laboratory reference range White blood cells (K/μL) 2300 - - 4400−11,000 Neutrophils (%) 79 - - 50−70 Lymphocytes (%) 8.5 - - 20−40 Hemoglobin (g/dL) 14 - - 14−17.5 Red blood cells (M/μL) 4.59 - - 4.1−5.1 Platelets 143,000 - - 150,000−440,000 Potassium (mmol/L) 3.5 3.7 4.4 3.60−5.00 Sodium (mmol/L) 142 137 141 135−150 BUN (mg/dL) 8 - 6 7−18.6 Creatinine (mg/dL) 1 - 1.1 0.7−1.3 Lactate dehydrogenase (U/L) 327 - - 100−480 Creatine phosphokinase (U/L) 124 - - 30−170 Alkaline phosphatase (U/L) 153 - - 100−240 Aspartate aminotransferase (U/L) 31 - - 15−59 Alanine aminotransferase (U/L) 49 - - 10−72 CRP (mg/L) 84 40 15 0.0−5.0 Arterial blood gas on air pH 7.40 - - pO 2 (mmHg) 61.3 - - pCO 2 (mmHg) 33.2 - - HCO 3 (mmol/L) 20.2 - - SaO 2 (%) 91 - - Urinalysis Negative - - pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
Complete laboratory examinations at the emergency department on the first visit and subsequent visits
pO 2 =Partial pressure of oxygen; pCO 2 =Partial pressure of carbon dioxide; HCO 3 =Bicarbonate; SaO 2 =Oxygen saturation; CRP=C-reactive protein; IVIG=Intravenous immunoglobulin; BUN=Blood urea nitrogen
The patient was admitted to the infectious disease ward. A chest CT scan demonstrated atypical pneumonia consistent with COVID-19 pneumonia. On day 1, he received remdesivir (200 mg loading dose followed by 100 mg daily for 5 days), intravenous dexamethasone (8 mg daily for 3 days), and empirical antibiotic therapy with levofloxacin and ampicillin. Despite 48 h of treatment, the patient remained febrile. All laboratory findings and elevated CRP are shown in Table 8 .
On day 3 of hospitalization, IVIG was added to his treatment regimen (with a single dose of 0.4 g/kg). His fever resolved within 24 h of IVIG administration, and he showed clinical improvement. By day 10, all clinical symptoms, including fever, had subsided, and CRP levels normalized. The patient was discharged 3 days after IVIG initiation following confirmation of sustained clinical recovery.
In Table 9 , a comparison between eight patients was made based on symptoms, paraclinical findings, and medication use.
Table 9 Compare 8 cases Case number Symptoms Duration symptoms First CRP Last CRP Medication 1 Fever, chills, dyspnea, arthralgia, generalized weakness 27 days 43 6 Remdesivir, intravenous dexamethasone, levofloxacin, linezolid, meropenem, IVIG 2 Fever, dyspnea, cough 16 days 128 44 Remdesivir, intravenous dexamethasone, methylprednisolone, levofloxacin ampicillin, IVIG 3 fever, chills 55 days 49 10 Remdesivir, intravenous dexamethasone, and prednisolone, IVIG 4 Fever, chills, dry cough, headache 17 days 79 28 Remdesivir, intravenous dexamethasone, prednisolone, IVIG 5 Severe cough, dyspnea 95 days 78 22 Remdesivir, intravenous dexamethasone, methylprednisolone, IVIG 6 Fever, dry cough, dyspnea 67 days 176 10 Remdesivir, intravenous dexamethasone, linezolid, piperacillin-tazobactam, IVIG 7 Fever, dyspnea, dry cough 26 days 60.3 3 Remdesivir, oral prednisolone, meropenem, levofloxacin, IVIG 8 High-grade fever, cough 10 days 84 15 Remdesivir, intravenous dexamethasone, levofloxacin, ampicillin, IVIG CRP=C-reactive protein; IVIG=Intravenous immunoglobulin
Compare 8 cases
CRP=C-reactive protein; IVIG=Intravenous immunoglobulin
Written informed consent has been taken from all patients, and the ethical code for this research is: IR.MUI.MED.REC.1403.436.
DISCUSSION
This study demonstrated that IVIG therapy significantly alleviates long COVID-19 symptoms in MS patients treated with rituximab. Elevated IgG levels and reduced inflammatory markers, such as CRP, indicate humoral immune reconstitution and diminished systemic inflammation. These findings align with the work of Thompson et al .,[ 12 ] who reported marked IgG improvement following IVIG.
While corticosteroids (e.g., dexamethasone) and remdesivir are standard therapies for severe COVID-19,[ 8 ] their efficacy is limited in patients with profound immune deficiencies, such as those on rituximab.[ 7 , 14 ] A cohort study of 150 MS patients revealed that remdesivir induced clinical improvement in only 22% of cases,[ 12 ] likely due to suppressed humoral immunity and impaired neutralizing antibody production.[ 15 ] Johnson et al .[ 9 ] found that rituximab-treated MS patients face a threefold higher risk of developing long COVID-19 compared to the general population. IVIG, however, reduced respiratory symptoms by 40% in these patients and doubled recovery rates compared to remdesivir in immunocompromised cohorts.[ 16 ] Martinez et al .[ 10 ] further confirmed IVIG’s effectiveness in mitigating chronic COVID-19 symptoms such as fatigue and dyspnea.
Rituximab disrupts IgG production by suppressing B cells.[ 4 , 9 ] In contrast, IVIG enhances antiviral immunity by replenishing polyclonal antibodies, curbing SARS-CoV-2 replication,[ 17 , 18 ] and attenuating pulmonary and neurological inflammation through inhibition of pro-inflammatory cytokines such as interleukin-6 and tumor necrosis factor-alpha.[ 15 , 19 ] IVIG also modulates macrophage overactivation by binding to Fcγ receptors.[ 20 ]
Multiple studies validate IVIG’s role in ameliorating long COVID-19 symptoms and restoring humoral immunity. For instance, Gelfand[ 11 ] demonstrated that IVIG elevates IgG levels and reduces systemic inflammation. In addition, IVIG promotes immune balance by expanding regulatory T-cells, thereby preventing cytokine storms.[ 19 ] Similar studies corroborate IVIG’s capacity to enhance antiviral responses and alleviate long COVID-19 manifestations.[ 18 , 21 ]
Clinical evidence suggests IVIG reduces long COVID-19-related hospitalization risks by 40% in MS patients.[ 18 , 22 , 23 ] Notably, in MS patients with IgG levels below 400 mg/dL, IVIG shortened symptom duration from 12 weeks to 4 weeks.[ 24 ]
CONCLUSION
IVIG holds significant potential for managing long COVID-19 in rituximab-treated MS patients. By improving immune parameters and reducing inflammation, IVIG could serve as an adjunctive strategy in therapeutic protocols for this population. However, further research is essential to determine optimal dosing, evaluate long-term effects, and analyze cost-effectiveness.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Conflicts of interest
There are no conflicts of interest.
Funding Statement
Nil.
REFERENCES