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1.
Mol Oncol ; 2022.
Article in English | PubMed | ID: covidwho-2157662

ABSTRACT

Patients with solid tumors have been a risk group since the beginning of the SARS-CoV-2 pandemic due to more significant complications, hospitalizations, or deaths. The immunosuppressive state of cancer treatments or the tumor itself could influence the development of post-vaccination antibodies. This study prospectively analyzed 89 patients under chemotherapy and/or immunotherapy, who received 2 doses of the mRNA-1237 vaccine, and were compared with a group of 26 non-cancer individuals. Information on adverse events and neutralizing antibodies against the ancestral strain of SARS-CoV-2 (WH1) have been analyzed. Local reactions accounted for 65%, while systemic reactions accounted for 46% of oncologic individuals/cancer patients . Regarding the response to vaccination, 6.7% of cancer patients developed low neutralizing antibody levels. Lower levels of neutralizing antibodies between cancer and non-cancer groups were significant in individuals without previous SARS-CoV-2 infection, but not in previously infected individuals. We also observed that patients receiving chemotherapy or chemoimmunotherapy have significantly lower levels of neutralizing antibodies than non-cancer individuals. In conclusion, our study confirms the importance of prioritizing cancer patients receiving anticancer treatment in SARS-CoV-2 vaccination programs.

2.
Open Forum Infectious Diseases ; 8(SUPPL 1):S369-S370, 2021.
Article in English | EMBASE | ID: covidwho-1746461

ABSTRACT

Background. There are few real-world data on the use of remdesivir (RDV) looking at timing of initiation in relation to symptom onset and severity of presenting disease. Methods. We conducted multi-country retrospective study of clinical practice and use of RDV in COVID-19 patients. De-identified medical records data were entered into an e-CRF. Primary endpoints were all-cause mortality at day 28 and hospitalization duration. We assessed time from symptom onset to RDV start and re-admission. We included adults with PCR-confirmed symptomatic COVID-19 who were hospitalized after Aug 31, 2020 and received at least 1 dose of RDV. Descriptive analyses were conducted. Kaplan-Meier methods were used to calculate the mortality rate, LogRank test to compare groups defined by severity of disease. Competing risk regression with discharge and death as competing events was used to estimate duration of hospitalization, and Gray's test to compare the groups. Results. 448 patients in 5 countries (12 sites) were included. Demographics are summarized (table) by 3 disease severity groups at baseline: no supplemental oxygen (NSO), low flow oxygen ≤6 L/min (LFO), and high-flow oxygen > 6L/min (HFO). No demographic differences were found between groups except for the higher percentage of cancer/chemotherapy patients in NSO group. Corticosteroids use was HFO 73.6%, LFO 62.7%, NSO 58.0%. Mortality rate was significantly lower in NSO, and LFO groups compared with HFO (6.2%, 10.2%, 23.6%, respectively;Fig1). Median duration of hospitalization was 9 (95%CI 8-10), 9 (8-9), 13 (10-15) days, respectively (Fig2). Median time from first symptom to RDV start was 7 days in all 3 groups. Patients started RDV on day 1 of hospitalization in HFO and LFO and day 2 on NSO groups. And received a 5 day course (median). Readmission within 28-days of discharge was < 5% and similar across all 3 groups. Conclusion. In this real-world cohort of COVID-19 positive hospitalized patients, RDV use was consistent across countries. RDV was started within a median of 7 days from symptom within 2 days of admission and given for a median of 5 days. Higher mortality rate and duration of hospitalization was seen in the HFO group and similar rates seen in the LFO and NSO groups. Readmission was consistently low across all 3 groups.

5.
Heart Rhythm ; 18(8):S166, 2021.
Article in English | EMBASE | ID: covidwho-1333454

ABSTRACT

Background: Persistent symptoms after the acute SARS-CoV-2 infection are referred to as post-COVID-19 syndrome(PCS). Fatigue, palpitations and exercise intolerance are common complains among PCS patients in whom unexplained sinus tachycardia is a frequent observation. Objective: To evaluate the prevalence and the pathophysiological mechanisms of IST in a consecutive and prospective population of patients with PCS. Methods: Consecutive patients with persistent symptoms 3 months after an acute COVID-19 were prospectively evaluated at a multi-disciplinary PCS unit. All patients were screened for IST and those with confirmed criteria underwent comprehensive CV examination: ECO, 24h Holter (assessment of the cardiac autonomic function), QoL Questionnaire (MLHFQ), six-min walking test (6MWT) and blood sample with inflammation and myocardial biomarkers. Two control patients, matched by age and gender, were assigned to each case: one with previous SARS-CoV-2 infection without PCS (group 2,recovered asymptomatic) and one without prior COVID (group 3,uninfected). Results: IST were met in 43/200 PCS patients (21%) being more common in young (mean age 39y) woman (91%) without clinical history and with mild COVID (not requiring hospital admission during the acute phase). Mean HR 96±3 (supine) and 112±17 (upright position), with 8 patients fulfilling diagnostic of POTS. No underlying structural heart disease, proinflammatory state, myocyte injury or hypoxia were identified 6MWT showed a significantly diminished exercise capacity(59% of the estimated distance). An impaired QoL was also identified. Regarding the 24h Holter, all HRV parameters were significantly deteriorated in IST patients compared with control groups (significantly decrease in time and frequency domain parameters). The most reduced components were those related with the cardiovagal tone: PNN50 4±4 in group 1 (vs 11±9 in group 2 and 18±9 in group 3;p<0 002);HF band 336±280 (vs 823±1200 in group 2 and 1229±630 in group 3;p=0 01). Conclusion: IST is a prevalent condition among PCS patients and may at least partially explain the prevalent symptoms of fatigue, impaired exercise, and palpitations, Cardiac ANS imbalance with decreased parasympathetic activity may account as a plausible explanation.

6.
Europace ; 23(SUPPL 3):iii126, 2021.
Article in English | EMBASE | ID: covidwho-1288010

ABSTRACT

Background: Persistent symptoms after the acute phase of SARS-CoV-2 infection are referred to as 'post-COVID-19 syndrome' (PCS), with a reported incidence ranging between 35% and 87%. Fatigue, palpitations and exercise intolerance are common complains among PCS patients in whom unexplained sinus tachycardia, occasionally exacerbated by postural changes, is a frequent observation that remains poorly characterized. Purpose: We sought to characterize the prevalence of inappropriate sinus tachycardia (IST) and postural orthostatic tachycardia (POTS) in a consecutive and prospective population of patients with PCS. Methods: Consecutive patients with persistent symptoms 3 months after an acute SARS-CoV-2 infection were prospectively evaluated at a multi-disciplinary PCS unit. All patients were screened for IST or POTS and those with confirmed criteria underwent comprehensive cardiovascular examination including echocardiography, 24-hour Holter, Minnesota Living with Heart Failure Questionnaire (MLHFQ), six-minute walking test (6MWT) and inflammation and myocardial biomarkers. Two control patients, matched by age and gender, were assigned to each case: one with previous SARS-CoV-2 infection without PCS (group 2) and one without prior SARS-CoV-2 infection (group 3). Results: IST or POTS criteria were met in 34 out of the 200 PCS patients (17%). The mean age was 39 ± 10 years, with 29 women (91%). The interval from the index COVID-19 disease to the PCS diagnosis was 71 ± 17 days, with a majority of patients (n = 29,85%) not requiring hospital admission during the acute phase. At physical examination, the mean heart rate was 96 ± 3bpm at supine and 112 ± 17bpm at the upright position, with 8 patients fulfilling diagnostic criteria of POTS. No underlying structural heart disease, pro-inflammatory state, myocyte injury or hypoxia were identified among our patient population. The 6MWT showed a significantly diminished exercise capacity with a 59% of the estimated distance after adjustment by age, sex and body mass index;an impaired quality of life was also identified, as suggested by a median MLFHQ total score of 67 out of 105 points. The 24-hour Holter showed an increase in HR predominantly during daytime in group 1 (mean daytime HR of 94 ± 3bpm), an altered heart rate variability with a decrease in time domain parameters [PNN50 4 ± 4 in group 1 (vs. 11 ± 9 in group 2 and 18 ± 9 in group 3;p < 0.002)respectively;SD 100 ± 20 (vs. 127 ± 38 and 136 ± 13;p = 0.009) and a decrease in frequency domain parameters [LF 751 ± 450 (vs. 1721 ± 1009 and 2199 ± 920;p = 0.01), HF 336 ± 280 (vs. 823 ± 1200 and 1229 ± 630;p = 0.01)]. Conclusions: IST and its POTS variant are a prevalent condition among PCS patients and may at least partially explain the common symptoms of fatigue, impaired exercise and palpitations that characterize the PCS. Cardiac autonomic nervous system imbalance may account as a plausible pathophysiological mechanism of IST in PCS patients.

7.
Topics in Antiviral Medicine ; 29(1):88, 2021.
Article in English | EMBASE | ID: covidwho-1250606

ABSTRACT

Background: One of the fundamental pillars of SARS-CoV-2 pandemic control and vaccine development is understanding mid-and long-term immunity. Early humoral response has been extensively studied, however data on what recovered individuals are still scarce and the most recent studies are based on few time points over time, which limits the comprehension of the longitudinal pattern of the potential changes. In this study we have evaluated the neutralizing activity and IgG antibody titer against SARS-CoV-2 in mild/ asymptomatic and hospitalized COVID-19 individuals, over a 6-month period. Methods: We have evaluated the kinetics of the humoral immune response in 210 individuals infected by SARS-CoV-2 covering the first and second waves of COVID-19 outbreak in Catalonia (Spain). IgG antibody titer was evaluated with an in-house sandwich ELISA against the S2 subunit, the binding domain receptor (RBD) and the nucleoprotein (NP) and the neutralizing activity was evaluated by a neutralization assay with HIV reporter pseudoviruses expressing SARS-CoV-2 S protein. Statistical analyses were carried out using mixed-effects non-linear and linear models. Results: Most study participants developed a neutralizing humoral response against SARS-CoV-2, however the maximum neutralization titer was 10-fold lower in mild/asymptomatic individuals compared to those with a more severe illness. We observed a slow and progressive decay of neutralizing activity in individuals with mild or asymptomatic disease throughout the 6-month period. In hospitalized individuals, half maximal neutralization activity was achieved on day 10 and showed an initial rapid decline that significantly slowed and remained nearly flat after day 80. Despite this, activity at six months remained higher in hospitalized individuals compared to mild symptomatic participants. On the other hand, we observed that IgG antibody titers against S2, RBD and NP had a more marked fall without showing differences in the decay pattern between individuals with different degree of severity of the disease. Conclusion: Our data suggest that the neutralizing activity remains relatively stable for more than 6 months despite the decline in IgG antibodies, suggesting that the quality of immune response evolves and allows maintaining the neutralizing activity despite the decay in antibody titers. Our results provide a more detailed picture of the behavior of the natural humoral immune response over time that complements the current evidence on mid-term immunity.

8.
Topics in Antiviral Medicine ; 29(1):90, 2021.
Article in English | EMBASE | ID: covidwho-1250361

ABSTRACT

Background: Many immune studies of SARS-CoV-2 (CoV-2) infection have focused on the generation of virus-specific as a means of protection. However, a small group of CoV-2 infected individuals called Non-seroconverters (NSC), do not generate antibodies but experience a mild or moderate disease course. Identifying mechanism of CoV-2 control in NSC may inform the development of novel therapeutics and vaccines approaches. Methods: We identified eleven CoV-2 NSC (3.6%) from the King-cohort study (PI-20-217). NSC were defined by a positive CoV-2 PCR at the time of diagnosis in the absence of IgG, IgA and IgM in serum and plasma measured by two independent ELISA techniques. For comparison, we identify groups of CoV-2 convalescent (n=15) and low-neutralizers (n=15). We measured T-cell responses to the CoV-2 Spike (S) and Nucleocapsid (NP) recombinant proteins in PBMCs by ELISPOT and flow cytometry. We combined T-cell surface and lineage markers together with PD-1, functional (TNF, IFN-y, and IL-2) and activation induced markers (AIM: CD25, CD137 and OX40). Results: We identified CoV-2 specific CD4+ and CD8+ T-cells against the S and the NP in NSC individuals. All NSC responded to S by production of one or more cytokine in either CD4+ or CD8+ T-cells, and 57% responded to NP. Specific-CD8+ T cells against S in NSC were characterized by IFN-y, and TNF production, and we observed higher levels of TNF production as compared to low neutralizers (p=0.02). No differences were found in IFN-y, IL-2 and TNF production in S-specific CD4+ T cells between groups, nor in NP CD8+ or CD4+ T-cell responses. The levels of CD137/OX40 in CD8+ and CD4+ T cells were significantly lower in NSC in response to S (p=0.006, and p=0.012). Also, lower levels of PD-1 were observed in CD8+ T cells in response to NP in NSC (p=0.017). Conclusion: We provide evidence of SARS-CoV2 cellular immunity in NSC individuals despite the absence of humoral neutralizing responses. CD8+ and CD4+ T cells against the S and NP were present in NSC and characterized by TNF production in CD8+ T-cells in responses to S when compared to low neutralizers. Decreased levels of activation markers were observed in NSCs following S and NP stimulation. We propose a protective role of cellular immunity in NSC potentially driven by preexisting cellular responses.

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