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1.
Int J Gen Med ; 14: 5111-5117, 2021.
Article in English | MEDLINE | ID: covidwho-1817643

ABSTRACT

INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) could be a predictive factor of severe COVID-19. However, most relevant studies are retrospective, and the optimal NLR cut-off point has not been determined. The objective of our research was identification and validation of the best NLR cut-off value on admission that could predict high in-hospital mortality in COVID-19 patients. METHODS: Medical files of all patients admitted for COVID-19 pneumonia in our dedicated COVID-units between March and April 2020 (derivation cohort) and between October and December 2020 (validation cohort) were reviewed. RESULTS: Two hundred ninety-nine patients were included in the study (198 in the derivation and 101 in the validation cohort, respectively). Youden's J statistic in the derivation cohort determined the optimal cut-off value for the performance of NLR at admission to predict mortality in hospitalized patients with COVID-19. The NLR cut-off value of 5.94 had a sensitivity of 62% and specificity of 64%. In ROC curve analysis, the AUC was 0.665 [95% CI 0.530-0.801, p= 0.025]. In the validation cohort, the best predictive cut-off value of NLR was 6.4, which corresponded to a sensitivity of 63% and a specificity of 64% with AUC 0.766 [95% CI 0.651-0.881, p <0.001]. When the NLR cut-off value of 5.94 was applied in the validation cohort, there was no significant difference in death and survival in comparison with the derivation NLR cut-off. Net reclassification improvement (NRI) analysis showed no significant classification change in outcome between both NLR cut-off values (NRI:0.012, p=0.31). CONCLUSION: In prospective analysis, an NLR value of 5.94 predicted high in-hospital mortality upon admission in patients hospitalized for COVID-19 pneumonia.

2.
Kidney Medicine ; : 100470, 2022.
Article in English | ScienceDirect | ID: covidwho-1805342

ABSTRACT

Rationale & Objective Neutralizing monoclonal antibody treatments have shown promising preliminary results in kidney transplant recipients infected with SARS-CoV-2. However, their efficacy in kidney transplant recipients infected with Omicron variant has not been reported yet. Study Design Single-center retrospective study. Setting & Participants We included all consecutive kidney transplant recipients treated with monoclonal antibodies for SARS-CoV-2 infection (positive polymerase chain reaction on nasopharyngeal swab) between June 10th 2021 and January 14th 2022. Forty-seven kidney transplant recipients were included. All patients had symptoms evolving for ≤ 7 days and no oxygen therapy need at monoclonal antibody infusion. Results Symptoms at diagnosis were mainly cough (n=25 [53%]) and fever (n=15 [32%]). Eighty-three percent of the cohort (n=39) had been vaccinated with at least 2 doses before infection, of whom 77% (n=30) had demonstrated a vaccine-induced humoral response. They were treated with either casirivimab-imdevimab (n= 16 [34%]) or sotrovimab (n= 31 [66%]) a median of 2 (ranges 0-6) days after the onset of symptoms. Except for one mild allergic reaction during casirivimab-imdevimab infusion, no side effects were reported. Median viral loads at admission (day 0) and 7 days after mAb infusion were 2,110,027 (ranges 1000-153,798,962) copies/mL and 1,000 (ranges 0-10,000,000) copies/mL, respectively. Genotypes were available for 22 kidney transplant recipients (47%). Omicron, Delta, and Gamma variants were identified in 13 (59%), 8 (36%), 1 (5%) patients, respectively. In kidney transplant recipients infected with Omicron variant, the median viral loads at day 0 and day 7 were 752,789 (ranges 4000-12,859,300) copies/mL and 1,353 (ranges 0-1,211,163) copies/mL, respectively. Two kidney transplant recipients required hospitalization immediately after sotrovimab perfusion for oxygen therapy that was weaned in 3 days allowing patients’ discharge. None were admitted to the intensive care unit or died. Limitations Small sample-size, no control group. Conclusions Neutralizing monoclonal antibody therapy is associated with positive outcomes in kidney transplant recipients with mild COVID-19, including those infected with the Omicron variant.

3.
Psychiatry Research Communications ; : 100037, 2022.
Article in English | ScienceDirect | ID: covidwho-1805006

ABSTRACT

Coronavirus disease 2019 has spread rapidly over the globe and has put an unprecedent psychological pressure on health care workers (HCWs). The present study aimed at quantifying the psychological consequences of the COVID-19 pandemic on HCWs during and after the first wave and identify sociodemographic, situational, and psychological risk/protective factors for symptoms severity. An online survey was sent by e-mail to all nurses and physicians employed by a teaching hospital in Brussels, Belgium. 542 (20,62%) completed the survey. 47%, 55%, 32% and 52% of participants reported posttraumatic stress, anxiety, depression and insomnia symptoms, respectively, during the peak. Two to three months later, posttraumatic symptoms emerged de novo in 54% of HCWs. It persisted in 89% of those presenting severe symptoms initially. Neuroticism was the strongest predictor of posttraumatic stress, anxiety, and insomnia. Work overload was the strongest predictor of depression and second predictor of posttraumatic stress, anxiety, and insomnia. Other significant predictors included being a nurse, the number of past traumatic experiences, avoidant coping style, and emotions ‘expression suppression.

4.
Travel Med Infect Dis ; 47: 102292, 2022 Mar 18.
Article in English | MEDLINE | ID: covidwho-1747538

ABSTRACT

BACKGROUND: Despite being a global pandemic, little is known about the factors influencing in-hospital mortality of COVID-19 patients in sub-Saharan Africa. This study aimed to provide data on in-hospital mortality among COVID-19 patients hospitalized in a single large center in Cameroon. METHODS: A hospital-based prospective follow-up was conducted from March 18 to June 30, 2020, including patients >18 years with positive PCR for SARS-COV-2 on nasopharyngeal swab admitted to the Laquintinie Douala hospital COVID unit. Predictors of in-hospital mortality were assessed using Kaplan Meir survival curves and Weibull regression for the accelerated time failure model. Statistical significance was considered as p < 0.05. RESULTS: Overall 712 patients (65,7% men) were included, mean age 52,80 ± 14,09 years. There were 580 (67,8% men) in-hospital patients. The median duration of hospital stay was eight days. The in-hospital mortality was 22.2%. Deceased patients compared to survivors were significantly older, had a higher temperature, respiratory rate, and heart rate, and lowest peripheral oxygen saturation at admission. After adjusting for age, sex, and other clinical patient characteristics, increased heart rate, increased temperature, decreased peripheral oxygen saturation. The critical clinical status was significantly associated with increased in-hospital mortality. In contrast, hospitalization duration greater than eight days and the use of hydroxychloroquine (HCQ) + azithromycin (AZM) therapy was associated with decreased risk of in-hospital mortality. CONCLUSION: One in five hospitalized COVID-19 patients die in a low-middle income setting. Critical clinical status, dyspnea, and increased heart rate were predictors of in-hospital mortality. This study will serve as a prerequisite for more robust subsequent follow-up studies. Also, these results will aid in revising national guidelines for the management of COVID-19 in Cameroon.

6.
J Public Health Afr ; 12(2): 1415, 2021 Dec 31.
Article in English | MEDLINE | ID: covidwho-1737144

ABSTRACT

At first less impacted than the rest of the world, African countries, including Cameroon, are also facing the spread of COVID-19. This study aimed to analyze the spread of the COVID-19 in Cameroon, one of the most affected countries in sub- Saharan Africa. We used the data from the Africa Centre for Disease Control and Prevention, reporting the number of confirmed cases and deaths, and analyzed the regularity of tests and confirmed cases and compared those numbers with neighboring countries. We tested different phenomenological models to model the early phase of the outbreak. Since the first reported cases on the 7th of March, 18,662 people have been diagnosed with COVID-19 as of the 24th of August, 186,243 tests have been performed, and 408 deaths have been recorded. New cases have been recorded only in 50% of the days since the first reported cases. There are considerable disparities in the reporting of daily cases, making it difficult to interpret these numbers and to model the evolution of the pandemic with the phenomenological models. Currently, following the finding from this study, it is challenging to predict the evolution of the pandemic and to make comparisons between countries as screening measures are so sparse. Monitoring should be performed regularly to provide a more accurate estimate of the situation and allocate healthcare resources more efficiently.

7.
J Med Virol ; 94(4): 1481-1487, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1718392

ABSTRACT

In-center maintenance hemodialysis (HD) patients are at high risk of acquiring coronavirus disease 2019 (COVID-19) by cross-contamination inside the unit. The aim of this study was to assess retrospectively the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission during the very first pandemic phase (March-July 2020) in a cohort of in-center maintenance HD patients and in nurses the same HD facility, using a phylogenetic approach. All SARS-CoV-2 quantitative reverse-transcription polymerase chain reaction positive patients and nurses from our HD unit-respectively 10 out of 98, and 8 out of 58- and two other positive patients dialyzed in our self-care unit were included. Whole-genome viral sequencing and phylogenetic analysis supported the cluster investigation. Five positive patients were usually dialyzed in the same room and same shift before their COVID-19 diagnosis was made. Viral sequencing performed on 4/5 patients' swabs showed no phylogenetic link between their viruses. The fifth patient (whose virus could not be sequenced) was dialyzed at the end of the dialysis room and was treated by a different nurse than the one in charge of the other patients. Three nurses shared the same virus detected in both self-care patients (one of them had been transferred to our in-center facility). The epidemiologically strongly suspected intra-unit cluster could be ruled out by viral genome sequencing. The infection control policy did not allow inter-patient contamination within the HD facility, in contrast to evidence of moderate dissemination within the nursing staff and in the satellite unit. Epidemiologic data without phylogenetic confirmation might mislead the interpretation of the dynamics of viral spreading within congregate settings.


Subject(s)
COVID-19/prevention & control , COVID-19/transmission , Infection Control/methods , Renal Dialysis , Aged , Belgium , COVID-19/epidemiology , COVID-19 Testing , Female , Genome, Viral , Humans , Kidney Failure, Chronic/therapy , Male , Middle Aged , Phylogeny , Retrospective Studies , SARS-CoV-2/genetics
8.
Transplant Direct ; 8(3): e1292, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1707294

ABSTRACT

Kidney transplant recipients (KTRs) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have an increased risk of mortality compared with the general population and hemodialysis patients. As these patients are immunosuppressed, it might seem obvious to attribute this excess mortality to the impaired immunity induced by immunosuppression. In line with this reasoning is the low immune response, both cellular and humoral, that KTRs mount in response to the anti-SARS-CoV-2 vaccine; however, acute respiratory distress syndrome associated with coronavirus disease 2019 is triggered by a state of inflammation and cytokine release syndrome that lead to pulmonary damage and increased mortality. In that context, immunosuppressive treatment dampening the immune response could, in theory, be potentially beneficial. This review aims at analyzing the current knowledge on the impact of immunosuppressive treatment on mortality in SARS-CoV-2-infected KTRs, the optimal management of immunosuppression in the coronavirus disease 2019 era, and the vaccine response and management in immunosuppressed KTRs.

9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-316442

ABSTRACT

Background: T he viral pandemic coronavirus disease 2019 (COVID-19) has disrupted cancer patient management around the world. Most reported data relate to incidence, risk factors, and outcome of severe COVID-19. The safety of systemic anti-cancer therapy in oncology patients with non-severe COVID-19 is unknown. Methods: ONCOSARS-1 was a prospective, single-center, academic observational study. Adult patients with solid tumors treated in the oncology day unit with systemic anti-cancer therapy during the initial phase of the COVID-19 pandemic in Belgium were included. All patients (n=363) underwent severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) serological testing after the peak of the pandemic in Belgium. Additionally, 141 of these patients also had a SARS-CoV-2 RT-PCR test during the pandemic. The main objective was to determine the safety of systemic cancer treatment, measured by the rate of adverse events according to the Common Terminology Criteria for Adverse Events, in SARS-CoV-2-positive patients compared with SARS-CoV-2-negative patients. Results: Twenty-two (6%) of the 363 eligible patients were positive for SARS-CoV-2 by RT-PCR and/or serology. Of these, three required transient oxygen supplementation, but none required admission to the intensive care unit. Hematotoxicity was the only adverse event more frequently observed in SARS-CoV-2 -positive patients than in SARS-CoV-2-negative patients: 73% vs 35% ( P <0.001). This association remained significant (odds ratio (OR) 4.1, P =0.009) even after adjusting for performance status and type of systemic treatment. Hematological adverse events led to more treatment delays for the SARS-CoV-2-positive group: 55% vs 20% ( P <0.001). Median duration of treatment interruption was similar between the two groups: 14 and 11 days, respectively. Febrile neutropenia, infections unrelated to COVID-19, and bleeding events occurred at a low rate in the SARS-CoV-2-positive patients. Conclusion: Systemic anti-cancer therapy appeared safe in ambulatory oncology patients treated during the COVID-19 pandemic. There were, however, more treatment delays in the SARS-CoV-2-positive population, mainly due to a higher rate of hematological adverse events.

10.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-309410

ABSTRACT

Background: The COVID-19 pandemic has imposed an enormous burden on health care systems around the world. In the past, the administration of convalescent plasma of patients having recovered from SARS and severe influenza to patients actively having the disease, showed promising effects on mortality and appeared safe. Whether or not this also holds true for the novel SARS-CoV-2 virus is currently unknown. Methods: DAWn-Plasma is a multicentre nation-wide, randomized, open-label, phase II proof-of-concept clinical trial, evaluating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19 in Belgium. Patients hospitalized with a confirmed diagnosis of COVID-19 are eligible when they are symptomatic (i.e. clinical or radiological signs) and have been diagnosed with COVID-19 in the 72 hours before study inclusion through a PCR (nasal/nasopharyngeal swab or bronchoalveolar lavage) or a chest-CT scan showing features compatible with COVID-19 in the absence of an alternative diagnosis. Patients are randomized in a 2:1 ratio to either standard of care and convalescent plasma (active treatment group) or standard of care only. The active treatment group receives 2 units of 200 to 250 mL of convalescent plasma within 12 hours after randomization, with a second administration of 2 units 24 to 36 hours after ending the first administration. The trial aims to include 483 patients and will recruit from 25 centres across Belgium. The primary endpoint is the proportion of patients that require mechanical ventilation or have died at day 15. The main secondary endpoints are clinical status on day 15 and day 30 after randomization, as defined by the WHO Progression 10-point ordinal scale, and safety of the administration of convalescent plasma. Discussion: This trial will either provide support or discourage the use of convalescent plasma as early intervention for the treatment of hospitalized patients with COVID-19 infection. Trial registration: Clinicaltrials.gov, Identifier: NCT04429854. Registered 12 June 2020 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04429854.

11.
J Gen Intern Med ; 37(5): 1226-1232, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1681684

ABSTRACT

BACKGROUND: Treating hypoxemia while meeting the soaring demands of oxygen can be a challenge during the COVID-19 pandemic. OBJECTIVE: To determine the efficacy of the surgical facemask and the double-trunk mask on top of the low-flow oxygen nasal cannula on arterial partial pressure of oxygen (PaO2) in hypoxemic COVID-19 patients. DESIGN: Randomized controlled trial. PARTICIPANTS: Hospitalized adults with COVID-19 and hypoxemia treated with the low-flow nasal cannula were enrolled between November 13, 2020, and March 05, 2021. INTERVENTIONS: Patients were randomized in a 1:1:1 ratio to receive either the nasal cannula alone (control) or the nasal cannula covered by the surgical facemask or the double-trunk mask. Arterial blood gases were collected at baseline and 30 min after the use of each system. The oxygen output was adapted afterwards to retrieve the baseline pulse oxygen saturation. The final oxygen output value was recorded after another 30-min period. MAIN MEASURES: The primary outcome was the absolute change in PaO2. Secondary outcomes included changes in oxygen output, arterial partial pressure of carbon dioxide (PaCO2), vital parameters, and breathlessness. KEY RESULTS: Arterial blood samples were successfully collected in 24/27 (8 per group) randomized patients. Compared to the nasal cannula alone, PaO2 increased with the surgical facemask (mean change: 20 mmHg, 95% CI: 0.7-38.8; P = .04) and with the double-trunk mask (mean change: 40 mmHg; 95% CI: 21-59; P < .001). Oxygen output was reduced when adding the surgical facemask (median reduction: 1.5 L/min [95% CI: 0.5-4.5], P < .001) or the double-trunk mask (median reduction: 3.3 L/min [95% CI: 2-5], P < .001). The double-trunk mask was associated with a PaCO2 increase of 2.4 mmHg ([95% CI: 0-4.7], P = .049). Neither mask influenced vital parameters or breathlessness. CONCLUSIONS: The addition of the surgical facemask or the double-trunk mask above the nasal cannula improves arterial oxygenation and reduces oxygen consumption.


Subject(s)
COVID-19 , Adult , Cannula , Humans , Masks , Oxygen , Pandemics
13.
Sci Rep ; 12(1): 2077, 2022 02 08.
Article in English | MEDLINE | ID: covidwho-1677267

ABSTRACT

More than a year after the start of the pandemic, COVID-19 remains a global health emergency. Although the immune response against SARS-CoV-2 has been extensively studied, some points remain controversial. One is the role of antibodies in viral clearance and modulation of disease severity. While passive transfer of neutralizing antibodies protects against SARS-CoV-2 infection in animal models, titers of anti-SARS-CoV-2 antibodies have been reported to be higher in patients suffering from more severe forms of the disease. A second key question for pandemic management and vaccine design is the persistence of the humoral response. Here, we characterized the antibody response in 187 COVID-19 patients, ranging from asymptomatic individuals to patients who died from COVID-19, and including patients who recovered. We developed in-house ELISAs to measure titers of IgG, IgM and IgA directed against the RBD or N regions in patient serum or plasma, and a spike-pseudotyped neutralization assay to analyse seroneutralization. Higher titers of virus-specific antibodies were detected in patients with severe COVID-19, including deceased patients, compared to asymptomatic patients. This demonstrates that fatal infection is not associated with defective humoral response. Finally, most of recovered patients still had anti-SARS-CoV-2 IgG more than 3 months after infection.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Immunity, Humoral , SARS-CoV-2/immunology , Adult , Aged , COVID-19/mortality , Female , Humans , Male , Middle Aged
14.
AIDS Res Ther ; 19(1): 3, 2022 01 14.
Article in English | MEDLINE | ID: covidwho-1631500

ABSTRACT

BACKGROUND: Data on the association of human immunodeficiency virus (HIV) infection with adverse outcomes in patients with COVID-19 are conflicting. This systematic review and meta-analysis aimed to summarize the available information on the risk of hospitalization, severe disease, and death attributable to HIV in patients with COVID-19. METHODS: PubMed, EMBASE, Web of Science, and SCOPUS were searched through October 25, 2021, to identify relevant studies, without language restriction. A random-effects model was used to pool estimates. RESULTS: We included 44 studies reporting information from 38,971,065 patients with COVID-19. The pooled prevalence of HIV among COVID-19 patients was 26.9 ‰ (95% CI 22.7-31.3) and was significantly higher in studies conducted in Africa compared to those conducted elsewhere (118.5‰ [95% CI 84.8-156.9, 11 studies] vs 10.9‰ [95% CI 8.8-13.2, 27 studies]). In pooled analyses of unadjusted odds ratio, HIV-positive individuals were more likely to be admitted to hospital (OR: 1.49; 95% CI 1.01-2.21, 6 studies) compared to HIV-negative individuals. In the adjusted (for age and sex) analyses, HIV was associated with an increased risk of death (hazard ratio: 1.76, 95% CI 1.31-2.35, 2 studies). However, HIV was not associated with the severity of the disease (OR: 1.28; 95% CI 0.77-2.13, 13 studies), or death (OR: 0.81; 95% CI 0.47; 1.41, 23 studies) in patients with COVID-19 in the meta-analysis of unadjusted odds ratio. CONCLUSION: Our findings suggest that patients with HIV have an increased risk of hospital admission for COVID-19. HIV seems to be independently associated with increased risk of mortality in COVID-19 patient in adjusted analysis. However, this evidence was derived from only two studies.


Subject(s)
COVID-19 , Coinfection , HIV Infections , Coinfection/epidemiology , HIV Infections/complications , HIV Infections/epidemiology , Humans , Odds Ratio , SARS-CoV-2
16.
J Med Virol ; 94(4): 1481-1487, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1527446

ABSTRACT

In-center maintenance hemodialysis (HD) patients are at high risk of acquiring coronavirus disease 2019 (COVID-19) by cross-contamination inside the unit. The aim of this study was to assess retrospectively the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission during the very first pandemic phase (March-July 2020) in a cohort of in-center maintenance HD patients and in nurses the same HD facility, using a phylogenetic approach. All SARS-CoV-2 quantitative reverse-transcription polymerase chain reaction positive patients and nurses from our HD unit-respectively 10 out of 98, and 8 out of 58- and two other positive patients dialyzed in our self-care unit were included. Whole-genome viral sequencing and phylogenetic analysis supported the cluster investigation. Five positive patients were usually dialyzed in the same room and same shift before their COVID-19 diagnosis was made. Viral sequencing performed on 4/5 patients' swabs showed no phylogenetic link between their viruses. The fifth patient (whose virus could not be sequenced) was dialyzed at the end of the dialysis room and was treated by a different nurse than the one in charge of the other patients. Three nurses shared the same virus detected in both self-care patients (one of them had been transferred to our in-center facility). The epidemiologically strongly suspected intra-unit cluster could be ruled out by viral genome sequencing. The infection control policy did not allow inter-patient contamination within the HD facility, in contrast to evidence of moderate dissemination within the nursing staff and in the satellite unit. Epidemiologic data without phylogenetic confirmation might mislead the interpretation of the dynamics of viral spreading within congregate settings.


Subject(s)
COVID-19/prevention & control , COVID-19/transmission , Infection Control/methods , Renal Dialysis , Aged , Belgium , COVID-19/epidemiology , COVID-19 Testing , Female , Genome, Viral , Humans , Kidney Failure, Chronic/therapy , Male , Middle Aged , Phylogeny , Retrospective Studies , SARS-CoV-2/genetics
17.
Int J Gen Med ; 14: 7895-7905, 2021.
Article in English | MEDLINE | ID: covidwho-1523543

ABSTRACT

BACKGROUND: Preliminary reports described a reduction in non-COVID admissions during the first wave of the pandemic including some of critical diseases such as cancer, myocardial and cerebral infarction. OBJECTIVE: The aim of our study was to evaluate the impact of the COVID-19 pandemic on non-COVID in-hospital admissions in a large academic center in Belgium. MATERIALS AND METHODS: We performed a retrospective study of non-COVID-19 in-hospital admissions during the first two waves of the COVID-19 pandemic. The average number of admissions per week in 2020 has been compared to that of the same period in 2019 and 2018. Comparisons were made first for all admissions, then by disease groups, using the classification of APRDRG, and then by diagnoses using ICD-10-CM classification. RESULTS: Overall in-hospital admissions were reduced by around 39% and 29% during the first and the second waves of the COVID-19 pandemic respectively compared to 2018 and 2019. No significant difference was found between the average number of admissions in the early-COVID and the pre-COVID baseline period during the two waves. The average number of admissions was significantly reduced in the peak-COVID period compared to the baseline (first wave: 332 versus 763 admissions/week, p<0.01, -57%; second wave: 496 versus 788 admissions/week, p<0.01, -37%), as well as in the late-COVID period compared to the baseline (first wave: 412 versus 763 admissions/week, p<0.01, -46%; second wave: 470 versus 788 admissions/week, p<0.01, -40%). Cancer, myocardial and cerebral infarction admissions were not statistically reduced during the the two waves of COVID pandemic compared to the pre-COVID period. CONCLUSION: Our study shows that non-COVID in-hospital admissions rates were substantially reduced during the first two waves of COVID-19 pandemic. In our study, cancer, myocardial and cerebral infarction admissions were not statistically reduced, which was not in accordance to what was described in the literature.

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