Immune Dysfunction and Multiple Treatment Modalities for the SARS-CoV-2 Pandemic: Races of Uncontrolled Running Sweat?

Kothari, Ashish; Singh,; Nath, Uttam Kumar; Kumar, Sandeep; Rai, Vineeta; Kaushal, Kanica; Omar, Balram Ji; Pandey, Anshuman; Jain, Neeraj

doi:10.3390/biology9090243

Cited by 8 publications

(5 citation statements)

References 130 publications

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“…[ 19 ]. SARS CoV-2 causes immune dysfunction or dysregulation leading to a decreased T-cell population which mostly affects the CD4+ CD8+ T-cell subset, induces lymphocytopenia, and eventually results in bacterial and fungal superinfection [ 20 ]. In the case of hematological malignancies, severe lymphopenia has earlier been established as a predicting risk factor for invasive mold disease as observed in patient No.…”

Section: Discussionmentioning

confidence: 99%

Mixed invasive fungal infections among COVID-19 patients

Singh¹,

Prasad²,

Panda³

et al. 2022

CMM

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Background and Purpose: The healthcare system in India collapsed during the second wave of the COVID-19 pandemic. A fungal epidemic was announced amid the pandemic with several cases of COVID-associated mucormycosis and pulmonary aspergillosis being reported. However, there is limited data regarding mixed fungal infections in COVID-19 patients. Therefore, we present a series of ten consecutive COVID-19 patients with mixed invasive fungal infections (MIFIs). Materials and Methods: Among COVID-19 patients hospitalized in May 2021 at a tertiary care center in North India, 10 cases of microbiologically confirmed COVID-19- associated mucormycosis-aspergillosis (CAMA) were evaluated. Results: All patients had diabetes and the majority of them were infected with severe COVID-19 pneumonia (6/10, 60%) either on admission or in the past month while two were each of moderate (20%) and mild (20%) categories of COVID-19; and were treated with steroid and cocktail therapy. The patients were managed with amphotericin-B along with surgical intervention. In total, 70% of all CAMA patients (Rhizopus arrhizus with Aspergillus flavus in seven and Aspergillus fumigatus complex in three patients) survived. Conclusion: The study findings reflected the critical importance of a high index of clinical suspicion and accurate microbiological diagnosis in managing invasive dual molds and better understanding of the risk and progression of MIFIs among COVID-19 patients. Careful scrutiny and identification of MIFIs play a key role in theimplementation of effective management strategies.

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Section: Discussionmentioning

confidence: 99%

Mixed invasive fungal infections among COVID-19 patients

Singh¹,

Prasad²,

Panda³

et al. 2022

CMM

Self Cite

View full text Add to dashboard Cite

show abstract

“…In this study, all patients suffered from COVID-associated pneumonitis either at admission or within the past one month suggesting that residual pathology from an initial infection by respiratory viral infections can directly damage airway epithelium and facilitate invasion of tissues by molds like Mucorales and Aspergillus spp [19]. SARS CoV-2 leads to immune dysfunction or dysregulation, leading to a decreased T-cell population, mostly affecting the CD4+ CD8+ T-cell subset and induces lymphocytopenia, thus giving way to bacterial and fungal superinfection [9,20]. In the case of hematological malignancies, severe lymphopenia has earlier been established as a predicting risk factor for invasive mold disease as was also observed in patient 10 in this study who had pancytopenia [21].…”

Section: Discussionmentioning

confidence: 99%

Mixed invasive molds among COVID-19 patients

Singh

Prasad

Panda

et al. 2021

Preprint

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Purpose: Due to surge in COVID cases during the second wave of the COVID pandemic, the healthcare system collapsed in India with shortage of hospital beds, injudicious use of steroids and other immunomodulators, and poor glycaemic monitoring among a population with pre-existing risk of diabetes. Fungal epidemic was announced amid COVID pandemic with several cases of COVID-associated mucormycosis and aspergillosis being reported. But, there is no data regarding mixed fungal infections in COVID patients. Materials and Methods: The study presented a series of ten consecutive cases with dual invasive molds in patients infected with SARS-CoV-2. Among patients hospitalized with the diagnosis of COVID in May 2021 at a tertiary care center in North India, ten microbiologically confirmed dual/mixed COVID-associated mucor-aspergillosis (CAMA) were evaluated. Results: All patients were diabetics with the majority having severe COVID pneumonia (6/10, 60%) either on admission or in the past one month, whilst two were each of moderate (20%) and mild (20%) categories of COVID. The patients were managed with amphotericin-B along with surgical intervention. In this case series, 70% of all CAMA (Rhizopus arrhizus with Aspergillus flavus in seven and Aspergillus fumigatus in three patients) patients survived, connoting the critical importance of a high index of clinical suspicion and accurate microbiological diagnosis for managing invasive molds. Conclusions: Mixed fungal infections i.e. CAMA during COVID and post-COVID periods may be an emerging disease. This outbreak is seen particularly in such patients with uncontrolled diabetes, on steroids, or cocktail therapy, or living in unhygienic environments. We believe that our findings would help gain a better insight into the risk and progression of invasive fungal mixed infections among COVID patients and thus play a pivotal role in diagnosing, classifying, and implementing an effective management strategy for treating similar cases in the future.

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“…Based on these clinical insights development of 'off-the-shelf' third-party allogeneic virusspecific T cell therapies can be a powerful tool to treat COVID-19 associated lyphophenia, which is currently not amenable to standard therapeutic strategies. Like the T cells, the role of NK cells in SARS-CoV-2 infections is currently being examined [16][17][18][19][20]. The rationale of using NK cells as a modality for immune therapy for COVID-19 is also being considered.…”

Section: Highlightsmentioning

confidence: 99%

Induced pluripotent stem cell-based disease modeling and prospective immune therapy for coronavirus disease 2019

et al. 2022

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The emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses a never before seen challenge to human health and economy. Considering its clinical impact with no streamlined therapeutic strategies in sight, it is crucial to understand the infection process of the SARS-CoV-2. Our nondescript knowledge of the foresaid mechanisms impedes development of alternative therapeutics to address the pandemic. This aspect can be addressed by modeling SARS-CoV-2 infection in the human context to facilitate drug screening and discovery. Human induced pluripotent stem cells (iPSCs) derived lung epithelial cells and organoids recapitulating the features and functionality of the alveolar cell types can serve as an in vitro human model and screening platform for SARS-CoV-2. Recent studies suggest an immune system asynchrony leading to compromised function and proportion of specific immune cell types in Coronavirus disease (COVID) -19 patients. Replenishing these specific immune cells may serve as useful effectors against SARS-CoV-2 infection. Here, we review protocols for deriving lung epithelial cells, alveolar organoids and specific immune cells types such as T- lymphocytes and natural killer (NK) cells from iPSCs with the aim to aid investigators to make relevant in vitro models of SARS-CoV-2 along with the possibility derive immune cells types to treat COVID-19.

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Immune Dysfunction and Multiple Treatment Modalities for the SARS-CoV-2 Pandemic: Races of Uncontrolled Running Sweat?

Cited by 8 publications

References 130 publications

Mixed invasive fungal infections among COVID-19 patients

Mixed invasive fungal infections among COVID-19 patients

Mixed invasive molds among COVID-19 patients

Induced pluripotent stem cell-based disease modeling and prospective immune therapy for coronavirus disease 2019

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