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1.
Clin Lymphoma Myeloma Leuk ; 22(8): e691-e707, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1763646

ABSTRACT

BACKGROUND: The humoral response to vaccination in individuals with lymphoid malignancies or those undergoing anti-CD20 antibody therapy is impaired, but details of the response to mRNA vaccines to protect against COVID-19 remain unclear. This systematic review and meta-analysis aimed to characterize the response to COVID-19 mRNA vaccines in patients with lymphoid malignancies or those undergoing anti-CD20 antibody therapy. MATERIALS AND METHODS: A literature search retrieved 52 relevant articles, and random-effect models were used to analyze humoral and cellular responses. RESULTS: Lymphoid malignancies and anti-CD20 antibody therapy for non-malignancies were significantly associated with lower seropositivity rates (risk ratio 0.60 [95% CI 0.53-0.69]; risk ratio 0.45 [95% CI 0.39-0.52], respectively). Some subtypes (chronic lymphocytic leukemia, treatment-naïve chronic lymphocytic leukemia, myeloma, and non-Hodgkin's lymphoma) exhibited impaired humoral response. Anti-CD20 antibody therapy within 6 months of vaccination decreased humoral response; moreover, therapy > 12 months before vaccination still impaired the humoral response. However, anti-CD20 antibody therapy in non-malignant patients did not attenuate T cell responses. CONCLUSION: These data suggest that patients with lymphoid malignancies or those undergoing anti-CD20 antibody therapy experience an impaired humoral response, but cellular response can be detected independent of anti-CD20 antibody therapy. Studies with long-term follow-up of vaccine effectiveness are warranted (PROSPERO registration number: CRD42021265780).


Subject(s)
COVID-19 , Leukemia, Lymphocytic, Chronic, B-Cell , Lymphoma, Non-Hodgkin , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Vaccines, Synthetic , mRNA Vaccines
2.
Front Microbiol ; 12: 651403, 2021.
Article in English | MEDLINE | ID: covidwho-1231355

ABSTRACT

Coronavirus disease 2019 (COVID-19) has caused serious public health, social, and economic damage worldwide and effective drugs that prevent or cure COVID-19 are urgently needed. Approved drugs including Hydroxychloroquine, Remdesivir or Interferon were reported to inhibit the infection or propagation of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), however, their clinical efficacies have not yet been well demonstrated. To identify drugs with higher antiviral potency, we screened approved anti-parasitic/anti-protozoal drugs and identified an anti-malarial drug, Mefloquine, which showed the highest anti-SARS-CoV-2 activity among the tested compounds. Mefloquine showed higher anti-SARS-CoV-2 activity than Hydroxychloroquine in VeroE6/TMPRSS2 and Calu-3 cells, with IC50 = 1.28 µM, IC90 = 2.31 µM, and IC99 = 4.39 µM in VeroE6/TMPRSS2 cells. Mefloquine inhibited viral entry after viral attachment to the target cell. Combined treatment with Mefloquine and Nelfinavir, a replication inhibitor, showed synergistic antiviral activity. Our mathematical modeling based on the drug concentration in the lung predicted that Mefloquine administration at a standard treatment dosage could decline viral dynamics in patients, reduce cumulative viral load to 7% and shorten the time until virus elimination by 6.1 days. These data cumulatively underscore Mefloquine as an anti-SARS-CoV-2 entry inhibitor.

3.
iScience ; 24(4): 102367, 2021 Apr 23.
Article in English | MEDLINE | ID: covidwho-1157438

ABSTRACT

Antiviral treatments targeting the coronavirus disease 2019 are urgently required. We screened a panel of already approved drugs in a cell culture model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and identified two new agents having higher antiviral potentials than the drug candidates such as remdesivir and chroloquine in VeroE6/TMPRSS2 cells: the anti-inflammatory drug cepharanthine and human immunodeficiency virus protease inhibitor nelfinavir. Cepharanthine inhibited SARS-CoV-2 entry through the blocking of viral binding to target cells, while nelfinavir suppressed viral replication partly by protease inhibition. Consistent with their different modes of action, synergistic effect of this combined treatment to limit SARS-CoV-2 proliferation was highlighted. Mathematical modeling in vitro antiviral activity coupled with the calculated total drug concentrations in the lung predicts that nelfinavir will shorten the period until viral clearance by 4.9 days and the combining cepharanthine/nelfinavir enhanced their predicted efficacy. These results warrant further evaluation of the potential anti-SARS-CoV-2 activity of cepharanthine and nelfinavir.

4.
日本皮膚科学会雑誌 ; 130(11):2385-2389, 2020.
Article in Japanese | J-STAGE | ID: covidwho-874986

ABSTRACT

A 40-year-old male developed a transient fever on the day before presentation to our hospital;then which itching developed over the entire body. Clinical examination revealed dark reddish erythema and papules scattered on the trunk and extremities, but concentrated on the back. A chest X-ray showed no abnormalities. Viral infection was suspected, with drug eruption considered as a reasonable differential diagnosis. When interviewed 5 days later, the patient reported a mild cough, and mentioned that a colleague at his workplace was suspected of having COVID-19. PCR confirmed SARS-CoV-2. In patients with COVID-19, a rash occasionally precedes respiratory symptoms. Such patients may initially consult a dermatologist, who must consider the possibility of COVID-19 on encountering maculopapular lesions of unknown etiology, and perform both in-depth interview and virological examination.

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