Viral load decrease in SARS-CoV-2 BA.1 and BA.2 Omicron sublineages infection after treatment with monoclonal antibodies and direct antiviral agents.

The efficacy on the Omicron variant of the approved early coronavirus disease-2019 (COVID-19) therapies, especially monoclonal antibodies, has been challenged by in vitro neutralization data, while data on in vivo antiviral activity are lacking. We assessed potential decrease from Day 1 to Day 7 viral load (VL) in nasopharyngeal swabs of outpatients receiving Sotrovimab, Molnupiravir, Remdesivir, or Nirmatrelvir/ritonavir for mild-to-moderate COVID-19 due to sublineages BA.1 or BA.2, and average treatment effect by weighted marginal linear regression models. A total of 521 patients (378 BA.1 [73%], 143 [27%] BA.2) received treatments (Sotrovimab 202, Molnupiravir 117, Nirmatrelvir/ritonavir 84, and Remdesivir 118): median age 66 years, 90% vaccinated, median time from symptoms onset 3 days. Day 1 mean VL was 4.12 log2 (4.16 for BA.1 and 4.01 for BA.2). The adjusted analysis showed that Nirmatrelvir/ritonavir significantly reduced VL compared to all the other drugs, except versus Molnupiravir in BA.2. Molnupiravir was superior to Remdesivir in both BA.1 and BA.2, and to Sotrovimab in BA.2. Sotrovimab had better activity than Remdesivir only against BA.1. Nirmatrelvir/ritonavir showed the greatest antiviral activity against Omicron variant, comparable to Molnupiravir only in the BA.2 subgroup. VL decrease could be a valuable surrogate of drug activity in the context of the high prevalence of vaccinated people and low probability of hospital admission.

Telemedicine During COVID-19 Pandemic: Lesson Learned from the Lazio Region Infectious Diseases and Emergency Department Network.

Telemedicine and teleconsultation can be powerful and useful tools for patients to hamper the physical barriers to access to health care services during COVID-19 pandemic. We describe the teleconsultation (TC) model in the Lazio Region. It uses a hub-and-spoke network system on geographic regional basis using a web based digital platform, termed ADVICE with the aim to connect regional Emergency Departments (EDs) and Infectious Diseases (ID) acute and critical care settings for patients with acute ID syndrome. Between January 2020 and June 2021, the ADVICE platform received 18.686 TCs: of them, 10838 requests (58%) were for ID TCs in 7996 patients, followed by 2555(13%) requests for trauma, 2286(12%) for acute complex syndrome and 1681 (8%) for Stroke TCs. Three quarter of ID TCs were requested for SARS-COV-2 infection, followed by sepsis management in 7% and tuberculosis in 6%. In 5416 TCs, 68%, diagnostic investigations and therapeutic prescriptions were recommended before admission, in 1941 TCs, 24%, the recommendation was patient admission and in 608 TCs, 7%, was to discharge patient at home. Telemedicine have ensured high-profile consultations for ID patients and during COVID-19 the use of this resource optimized clinical patient management.

Legionella pneumonia: increased risk after COVID-19 lockdown? Italy, May to June 2020.

We report a case of Legionella pneumonia in a dishwasher of a restaurant in Rome, Italy, just after the end of the lockdown that was in place to control the SARS-CoV-2 epidemic. The case highlights the importance of strict monitoring of water and air systems immediately before reopening business or public sector buildings, and the need to consider Legionella infections among the differential diagnosis of respiratory infections after lockdown due to the ongoing COVID-19 pandemic.

Remission of an HHV8-related extracavitary primary effusion lymphoma in an HIV-positive patient during antiretroviral treatment containing dolutegravir.

BACKGROUND: Human herpes virus 8 (HHV8) is the causative agent of Kaposi's sarcoma and has been associated with an increasing number of hematologic diseases such as primary effusion lymphoma (PEL) (both classic and extracavitary form), multicentric Castleman disease and the germinotropic lymphoproliferative disorder. PEL is a rare B cell non-Hodgkin lymphoma that primarily affects immunocompromised patients; aggressive chemotherapy and antiretroviral therapy (ART) with protease inhibitors have been used, with poor results. We present a case of extracavitary PEL in an HIV-infected patient, regressed after ART initiation. CASE PRESENTATION: A 42-year-old male was admitted to the emergency room because of several months of malaise, fever and progressive deterioration of the general conditions. On physical examination soft non-painful subcutaneous masses were palpable at retronuchal, retroauricolar and thoracic regions. HIV serology resulted positive: HIV plasma viremia was 782,270 copies/mL, CD4 103 cells/mL. The excision of one of the masses, metabolically active at a positron emission tomography (PET-CT) scan, revealed an HHV8-related extracavitary PEL. HHV8 plasma viremia was 44,826 copies/mL. ART with tenofovir alafenamide/emtricitabine/dolutegravir was started together with ganciclovir for cytomegalovirus chorioretinitis. The progressive disappearance of the masses was seen after 6 weeks of ART, and a PET-CT scan resulted completely negative at 3 months. After 19 months of ART the patient was in remission of PEL, HIV viremia was undetectable (< 20 copies/mL), CD4 count was 766 cells/mL and HHV8 viremia was undetectable. CONCLUSIONS: In this clinical case, the complete regression of PEL has been achieved after the immune recovery, as a consequence of ART introduction, without chemotherapy. It cannot be excluded that ganciclovir, used for the treatment of CMV chorioretinitis, may have contributed to the control of HHV8 replication. Whether to try or not a conservative approach in HIV-infected PEL patients must be carefully evaluated, considering the patient's characteristics and the prognostic factors.

Comparative Evaluation of Subtyping Tools for Surveillance of Newly Emerging HIV-1 Strains.

HIV-1 non-B subtypes/circulating recombinant forms (CRFs) are increasing worldwide. Since subtype identification can be clinically relevant, we assessed the added value in HIV-1 subtyping using updated molecular phylogeny (Mphy) and the performance of routinely used automated tools. Updated Mphy (2015 updated reference sequences), used as a gold standard, was performed to subtype 13,116 HIV-1 protease/reverse transcriptase sequences and then compared with previous Mphy (reference sequences until 2014) and with COMET, REGA, SCUEAL, and Stanford subtyping tools. Updated Mphy classified subtype B as the most prevalent (73.4%), followed by CRF02_AG (7.9%), C (4.6%), F1 (3.4%), A1 (2.2%), G (1.6%), CRF12_BF (1.2%), and other subtypes (5.7%). A 2.3% proportion of sequences were reassigned as different subtypes or CRFs because of misclassification by previous Mphy. Overall, the tool most concordant with updated Mphy was Stanford-v8.1 (95.4%), followed by COMET (93.8%), REGA-v3 (92.5%), Stanford-old (91.1%), and SCUEAL (85.9%). All the tools had a high sensitivity (≥98.0%) and specificity (≥95.7%) for subtype B. Regarding non-B subtypes, Stanford-v8.1 was the best tool for C, D, and F subtypes and for CRFs 01, 02, 06, 11, and 36 (sensitivity, ≥92.6%; specificity, ≥99.1%). A1 and G subtypes were better classified by COMET (92.3%) and REGA-v3 (98.6%), respectively. Our findings confirm Mphy as the gold standard for accurate HIV-1 subtyping, although Stanford-v8.1, occasionally combined with COMET or REGA-v3, represents an effective subtyping approach in clinical settings. Periodic updating of HIV-1 reference sequences is fundamental to improving subtype characterization in the context of an effective epidemiological surveillance of non-B strains.

Structural equation modelling of viral tropism reveals its impact on achieving viral suppression within 6 months in treatment-naive HIV-1-infected patients after combination antiretroviral therapy.

OBJECTIVES: To evaluate the role of pre-treatment co-receptor tropism of plasma HIV on the achievement of viral suppression (plasma HIV RNA 1.69 log10 copies/mL) at the sixth month of combination antiretroviral therapy (cART) in a cohort of naive patients using, for the first time in this context, a path analysis (PA) approach. PATIENTS AND METHODS: Adult patients with chronic infection by subtype B HIV-1 were consecutively enrolled from the start of first-line cART (T0). Genotypic analysis of viral tropism was performed on plasma and interpreted using the bioinformatic tool Geno2pheno, with a false positive rate of 10%. A Bayesian network starting from the viro-immunological data at T0 and at the sixth month of treatment (T1) was set up and this model was evaluated using a PA approach. RESULTS: A total of 262 patients (22.1% bearing an X4 virus) were included; 178 subjects (67.9%) achieved viral suppression. A significant positive indirect effect of bearing X4 virus in plasma at T0 on log10 HIV RNA at T1 was detected (P = 0.009), the magnitude of this effect was, however, over 10-fold lower than the direct effect of log10 HIV RNA at T0 on log10 HIV RNA at T1 (P = 0.000). Moreover, a significant positive indirect effect of bearing an X4 virus on log10 HIV RNA at T0 (P = 0.003) was apparent. CONCLUSIONS: PA overcame the limitations implicit in common multiple regression analysis and showed the possible role of pre-treatment viral tropism at the recommended threshold on the outcome of plasma viraemia in naive patients after 6 months of therapy.

Dengue fever as autochthonous infectious disease in Italy: Epidemiological, clinical and virological characteristics.

BACKGROUND: Since August to November 2023, 82 cases of autochthonous or non-travel related Dengue virus (DENV) infection have been reported in Italy, highlighting a concerning trend of local transmission. We describe the clinical and laboratory findings of 10 autochthonous DENV in the metropolitan area of Rome admitted to the Lazzaro Spallanzani National Institute for Infectious Diseases. METHOD AND RESULTS: Ten patients (3 males, 7 females; median age: 51) with classic dengue fever symptoms were admitted between August and November 2023. Laboratory tests confirmed dengue infection through DENV non-structural protein 1 and/or immunoglobulins (IgM/IgG) positive tests, moreover leukopenia, thrombocytopenia, elevated transaminases were detected. A subset of patients underwent extensive biological sampling, including real-time RT-PCR and immunofluorescence, to monitor DENV-RNA and antibody levels over 30 days. DENV-1 was detected in 8 patients and DENV-3 in 2. Upon admission specific IgM antibodies were found in 7 patients while IgG antibodies in 4 patients. DENV RNA was consistently detected in blood within the first 8 days but was less common in saliva and urine. No DENV RNA was detected after day 24. CONCLUSION: These findings contribute to the understanding of the clinical course of DENV infection in a non-endemic setting as integrated epidemiological and clinical model to increase syndromic surveillance and timely diagnosis of DENV infections.

Immunological signature in human cases of monkeypox infection in 2022 outbreak: an observational study.

BACKGROUND: An unprecedented global monkeypox outbreak started in May, 2022. No data are yet available about the dynamics of the immune response against monkeypox virus. The aim of this study was to describe kinetics of T-cell response, inflammatory profile, and pox-specific T-cell induction in patients with laboratory-confirmed monkeypox. METHODS: 17 patients with laboratory-confirmed monkeypox admitted at the Lazzaro Spallanzani National Institute for Infectious Diseases (Rome, Italy), from May 19, to July 7, 2022, were tested for differentiation and activation profile of CD4 and CD8 T (expression of CD38, PD-1, and CD57 assessed by flow cytometry), frequency of pox-specific T cells (by standard interferon-γ ELISpot), and release of interleukin (IL)-1ß, IL-6, IL-8, and tumour necrosis factor (TNF) in plasma (by ELISA). All patients were tested 10-12 days after symptoms onset. In a subgroup of nine patients with a laboratory-confirmed monkeypox, the kinetics of the immune response were analysed longitudinally according to timing from symptoms onset and compared with ten healthy donors (ie, health-care workers recruited from the same institution). FINDINGS: Among the 17 patients, ten were HIV negative and seven HIV positive, all with good viro-immunological status. On days 0-3 from symptom onset, patients with laboratory-confirmed monkeypox were characterised by a statistically significant reduction in CD4+ T cells (p=0·0011) and a concurrent increase of CD8+ T cells (p=0·0057) compared with healthy donors. A lower proportion of naive (CD45RA+CD27+) CD4+ T cells was observed in six (67%) of nine patients and a concomitant higher proportion of effector memory (CD45RA-CD27-) CD4+ T cells in all patients; this skewed immune profile tended to normalise over time. A similar differentiated profile was also observed in CD8+ T cells with a consistent expansion of terminally differentiated CD8+ T cells. Patients with monkeypox had a higher proportion of CD4+CD38+ and CD38+CD8+ T-cells than healthy donors, which normalised after 12-20 days from symptom onset. The expression of PD-1 and CD57 on CD4+ and CD8+ T-cells showed kinetics similar to that observed for CD38. Furthermore, the inflammatory cytokines (IL-1ß, IL-6, IL-8, and TNF) were higher in patients with monkeypox than in healthy donors and, although they decreased over time, they remained elevated after recovery. Almost all patients (15 [94%] of 16) developed a pox-specific Th1 response. No differences in immune cells profile were observed between patients with and without HIV, whereas paucysimptomatic patients (without systemic symptoms, with less than five skin lesions, and no other mucosal localisation of monkeypox) showed a less perturbed immune profile early after symptom onset. INTERPRETATION: Our data showed the immunological signature of monkeypox virus infection, characterised by an early expansion of activated effector CD4+ and CD8+ T cells that persisted over time. Almost all patients, even regardless of HIV infection, developed a poxvirus-specific Th1 cell response. These results might have implications on the expected immunogenicity of monkeypox vaccination, suggesting that it might not be necessary to vaccinate people who have already been infected. FUNDING: Italian Ministry of Health. TRANSLATION: For the Italian translation of the abstract see Supplementary Materials section.

Lymphofollicular lesions associated with monkeypox (Mpox) virus proctitis.

In the recent 2022 monkeypox (Mpox) global outbreak, cases have been mostly documented among men who have sex with men. Proctitis was reported in almost 14% of cases. In this study, four Mpox-confirmed cases requiring hospitalizations for severe proctitis were characterized by clinical, virological, microbiological, endoscopic, and histological aspects. The study showed the presence of lymphofollicular lesions associated with Mpox virus rectal infection for the first time.

Sarilumab plus standard of care vs standard of care for the treatment of severe COVID-19: a phase 3, randomized, open-labeled, multi-center study (ESCAPE study).

Background: Among interleukin-6 inhibitors suggested for use in COVID-19, there are few robust evidences for the efficacy of sarilumab. Herein, we evaluated the efficacy and safety of sarilumab in severe COVID-19. Methods: In this phase 3, open-labeled, randomized clinical trial, conducted at 5 Italian hospitals, adults with severe COVID-19 pneumonia (excluding mechanically ventilated) were randomized 2:1 to receive intravenous sarilumab (400 mg, repeatable after 12 h) plus standard of care (SOC) (arm A) or to continue SOC (arm B). Randomization was web-based. As post-hoc analyses, the participants were stratified according to baseline inflammatory parameters. The primary endpoint was analysed on the modified Intention-To-Treat population, including all the randomized patients who received any study treatment (sarilumab or SOC). It was time to clinical improvement of 2 points on a 7-points ordinal scale, from baseline to day 30. We used Kaplan Meier method and log-rank test to compare the primary outcome between two arms, and Cox regression stratified by clinical center and adjusted for severity of illness, to estimate the hazard ratio (HR). The trial was registered with EudraCT (2020-001390-76). Findings: Between May 2020 and May 2021, 191 patients were assessed for eligibility, of whom, excluding nine dropouts, 176 were assigned to arm A (121) and B (55). At day 30, no significant differences in the primary endpoint were found (88% [95% CI 81-94] in arm A vs 85% [74-93], HR 1.07 [0.8-1.5] in arm B; log-rank p = 0.50). After stratifying for inflammatory parameters, arm A showed higher probability of improvement than B without statistical significance in the strata with C reactive protein (CRP) < 7 mg/dL (88% [77-96] vs 79% [63-91], HR 1.55 [0.9-2.6]; log-rank p = 0.049) and in the strata with lymphocytes <870/mmc (90% [79-96]) vs (73% [55-89], HR 1.53 [0.9-2.7]; log-rank p = 0.058). Overall, 39/121 (32%) AEs were reported in arm A and 14/55 (23%) in B (p = 0.195), while serious AEs were 22/121 (18%) and 7/55 (11%), respectively (p = 0.244). There were no treatment-related deaths. Interpretation: The efficacy of sarilumab in severe COVID-19 was not demonstrated both in the overall and in the stratified for severity analysis population. Exploratory analyses suggested that subsets of patients with lower CRP values or lower lymphocyte counts might have had benefit with sarilumab treatment, but this finding would require replication in other studies. The relatively low rate of concomitant corticosteroid use, could partially explain our results. Funding: This study was supported by INMI "Lazzaro Spallanzani" Ricerca Corrente Linea 1 on emerging and reemerging infections, funded by Italian Ministry of Health.

Nevirapine use, prolonged antiretroviral therapy and high CD4 nadir values are strongly correlated with undetectable HIV-DNA and -RNA levels and CD4 cell gain.

OBJECTIVES: To evaluate the correlations of the combination of undetectable HIV-DNA (<10 copies/10(6) peripheral blood mononuclear cells) and HIV-RNA (<1 copy/mL of plasma) levels and a CD4 cell count of >500 cells/mm(3) (defined as the treatment goal) in a group of 420 antiretroviral treatment (ART) responder patients. METHODS: A cross-sectional, open-label, multicentre trial was conducted in a cohort of 420 HIV-infected ART-treated subjects with viral loads persistently <50 copies/mL for a median observation time of 28.8 months. HIV-DNA and residual viraemia values and demographic, virological and immunological data were collected for each subject. RESULTS: Undetectable HIV-DNA was found in 16.6% (70/420) of patients and was significantly correlated with undetectable (<1 copy/mL) plasma viraemia (P = 0.0001). Higher CD4 cell count nadir (P < 0.001), a lower HIV-RNA viraemia at the start of treatment (P = 0.0016) and nevirapine use (P < 0.001) were correlated with an undetectable value of HIV-RNA. Twenty-six out of 420 patients (6.2%) reached the treatment goal. In multivariate analysis, higher nadir CD4 cell count (OR 3.86, 95% CI 1.47-10.16, P = 0.006), the duration of therapy (OR 1.07, 95% CI 1.02-1.12, P = 0.004) and the use of nevirapine (OR 2.59, 95% CI 1.07-6.28, P = 0.034) were independently related to this condition. CONCLUSIONS: Only 6.2% of ART-responder patients presented the combination of three laboratory markers that identified them as full responders. These results indicate the high variability of the ART-responding population and lead us to suggest caution in the selection of patients for possible simplification regimens.

Performance of genotypic tropism testing on proviral DNA in clinical practice: results from the DIVA study group.

OBJECTIVE: The DIVA study is aimed at setting up a standardized genotypic tropism-testing on proviral-DNA for the routine clinical diagnostic-laboratory. METHODS: Twelve local centres and 5 reference centres (previously cross-validated) were identified. For inter-center validation-procedure, 60 peripheral-blood mononuclear cells (PBMCs) aliquots from 45 HAART-treated patients were randomly chosen for population V3 sequencing on proviral-DNA at local HIV centre and at reference-laboratory. Viral tropism was predicted by Geno2Pheno algorithm (False Positive Rate [FPR] = 20%) as proposed by the European-Guidelines. Quantification of total HIV-1 DNA was based on a method described by Viard (2004). RESULTS: Quantification of HIV-1 DNA was available for 35/45 (77.8%) samples, and gave a median value of 598 (IQR:252- 1,203) copies/10 PBMCs. A total of 56/60 (93.3%) samples were successfully amplified by both the reference and the local virological centers. The overall concordance of tropism prediction between local and reference centers was 54/56 (96.4%). Results of tropism prediction by local centers were: 33/54 (61.1%) R5 and 21/54 (38.9%) X4/DM. CONCLUSION: There was high concordance in the genotypic tropism prediction based on proviral DNA among different virological centers throughout Italy. Our results are in line with other European studies, and support the use of genotypic tropism testing on proviral DNA in patients with suppressed plasma HIV-1 RNA candidate to CCR5-antagonist treatment.

Clinical Management of Patients With B-Cell Depletion Agents to Treat or Prevent Prolonged and Severe SARS-COV-2 Infection: Defining a Treatment Pathway.

Introduction: Immunocompromised patients with B-cell depletion agents are at risk for persistence and/or severe SARS-COV-2 infection. We describe a case series of 21 COVID-19 patients under B cell depletion therapy, mostly treated with a combined therapy based on intravenous remdesevir (RDV) and steroid associated with SARS-CoV-2 monoclonal antibodies against Spike glycoprotein and/or hyper-immune convalescent plasma. Methods: This is a single-center longitudinal study. We retrospectively enrolled a total number of 21 B-cell depleted consecutive hospitalized patients with COVID-19 at the Lazzaro Spallanzani National Institute for Infectious Diseases, Rome, Italy, from November 2020 to December 2021. Demographic characteristics, medical history, clinical presentation, treatment, adverse drug reactions, and clinical and virological outcome were collected for all patients. In a subgroup, we explore immune T cells activation, T cells specific anti-SARS-COV-2 response, and neutralizing antibodies. Results: Twenty-one inpatients with B-cell depletion and SARS-COV-2 infection were enrolled. A median of 1 B cells/mm3 was detected. Eighteen patients presented hypogammaglobulinemia. All patients presented interstitial pneumonia treated with intravenous RDV and steroids. Sixteen patients were treated with monoclonal antibodies against SARS-CoV-2 Spike protein, four patients were treated with SARS-CoV-2 hyper-immune convalescent plasma infusion, and three patients received both treatments. A variable kinetic of T cell activation returning to normal levels at Day 30 after immunotherapy infusion was observed. All treated patients recovered. Conclusion: In COVID-19 immunosuppressed subjects, it is mandatory to establish a prompt, effective, and combined multi-target therapy including oxygen, antiviral, steroid, and antibody-based therapeutics, tailored to the patient's clinical needs.

The first case of meningitis associated with SARS-CoV-2 BA.2 variant infection with persistent viremia.

Severe neurological disorders and vascular events during COVID-19 have been described. Here, we describe the first case of a female patient infected with the SARS-CoV-2 BA.2 Omicron variant of concern with meningitis with newly diagnosed central demyelinating disease.

Kinetics of the B- and T-Cell Immune Responses After 6 Months From SARS-CoV-2 mRNA Vaccination in Patients With Rheumatoid Arthritis.

Objective: To assess the kinetics of the humoral and cell-mediated responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in rheumatoid arthritis (RA) patients treated with different immunosuppressive therapies. Methods: Following vaccine completed schedule, health care workers (HCWs, n = 49) and RA patients (n = 35) were enrolled at 5 weeks (T1) and 6 months (T6) after the first dose of BNT162b2-mRNA vaccination. Serological response was assessed by quantifying anti-receptor-binding domain (RBD)-specific immunoglobulin G (IgG) and SARS-CoV-2 neutralizing antibodies, while cell-mediated response was assessed by a whole-blood test quantifying the interferon (IFN)-γ response to spike peptides. B-cell phenotype and IFN-γ-specific T-cell responses were evaluated by flow cytometry. Results: After 6 months, anti-RBD antibodies were still detectable in 91.4% of RA patients, although we observed a significant reduction of the titer in patients under Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4)-Ig [median: 16.4 binding antibody units (BAU)/ml, interquartile range (IQR): 11.3-44.3, p < 0.0001] or tumor necrosis factor (TNF)-α inhibitors (median: 26.5 BAU/ml, IQR: 14.9-108.8, p = 0.0034) compared to controls (median: 152.7 BAU/ml, IQR: 89.3-260.3). All peripheral memory B-cell (MBC) subpopulations, in particular, the switched IgG+ MBCs (CD19+CD27+IgD-IgM-IgG+), were significantly reduced in RA subjects under CTLA-4-Ig compared to those in HCWs (p = 0.0012). In RA patients, a significantly reduced anti-RBD IgG titer was observed at T6 vs. T1, mainly in those treated with CTLA-4-Ig (p = 0.002), interleukin (IL)-6 inhibitors (p = 0.015), and disease-modifying antirheumatic drugs (DMARDs) ± corticosteroids (CCSs) (p = 0.015). In contrast, a weak nonsignificant reduction of the T-cell response was reported at T6 vs. T1. T-cell response was found in 65.7% of the RA patients at T6, with lower significant magnitude in patients under CTLA-4-Ig compared to HCWs (p < 0.0001). The SARS-CoV-2 IFN-γ-S-specific T-cell response was mainly detected in the CD4+ T-cell compartment. Conclusions: In this study, in RA patients after 6 months from COVID-19 vaccination, we show the kinetics, waning, and impairment of the humoral and, to a less extent, of the T-cell response. Similarly, a reduction of the specific response was also observed in the controls. Therefore, based on these results, a booster dose of the vaccine is crucial to increase the specific immune response regardless of the immunosuppressive therapy.

Prolonged and severe SARS-CoV-2 infection in patients under B-cell-depleting drug successfully treated: A tailored approach.

Prolonged B-cell depletion due to anti-CD20 monoclonal antibody (mAbs) therapy impairs the adaptive immune response, causing severe manifestations during COronaVIrus Disease-2019 (COVID-19). The cases of two patients under anti-CD20 therapy who experienced prolonged and severe COVID-19 successfully treated with mAbs against Severe Acute Respiratory Syndrome-CoV-2 spike proteins are reported.