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1.
Microorganisms ; 10(1)2022 Jan 04.
Article in English | MEDLINE | ID: covidwho-1637975

ABSTRACT

Infectious disease outbreaks had a significant impact on shaping the societies and cultures throughout human history [...].

3.
Open Forum Infect Dis ; 9(1): ofab588, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1608344

ABSTRACT

Background: Therapeutic options for hospitalized patients with severe coronavirus disease 2019 (sCOVID-19) are limited. Preliminary data have shown promising results with baricitinib, but real-life experience is lacking. We assessed the safety and effectiveness of add-on baricitinib to standard-of-care (SOC) including dexamethasone in hospitalized patients with sCOVID-19. Methods: This study is a 2-center, observational, retrospective cohort study of patients with sCOVID-19, comparing outcomes and serious events between patients treated with SOC versus those treated with SOC and baricitinib combination. Results: We included 369 patients with sCOVID-19 (males 66.1%; mean age 65.2 years; median symptom duration 6 days). The SOC was administered in 47.7% and combination in 52.3%. Patients treated with the combination reached the composite outcome (intensive care unit [ICU] admission or death) less frequently compared with SOC (22.3% vs 36.9%, P = .002). Mortality rate was lower with the combination in the total cohort (14.7% vs 26.6%, P = .005), and ICU admission was lower in patients with severe acute respiratory distress syndrome (29.7% vs 44.8%, P = .03). By multivariable analysis, age (odds ratio [OR] = 1.82, 95% confidence interval [CI] = 1.36-2.44, per 10-year increase), partial pressure of oxygen/fraction of inspired oxygen ratio (OR = 0.60, 95% CI = .52-0.68, per 10 units increase), and use of high-flow nasal cannula (OR = 0.34; 95% CI, .16-0.74) were associated with the composite outcome, whereas baricitinib use was marginally not associated with the composite outcome (OR = 0.52; 95% CI, .26-1.03). However, baricitinib use was found to be significant after inverse-probability weighted regression (OR = 0.93; 95% CI, .87-0.99). No difference in serious events was noted between treatment groups. Conclusions: In real-life settings, addition of baricitinib to SOC in patients hospitalized with sCOVID-19 is associated with decreased mortality without concerning safety signals.

4.
Neurology ; 97(21): e2136-e2147, 2021 11 23.
Article in English | MEDLINE | ID: covidwho-1596718

ABSTRACT

BACKGROUND AND OBJECTIVES: There is accumulating evidence supporting an association between the thrombosis and thrombocytopenia syndrome (TTS) and adenovirus vector-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Yet TTS and TTS-associated cerebral venous sinus thrombosis (CVST) remain poorly characterized. We aim to systematically evaluate the proportion of CVST among TTS cases and assess its characteristics and outcomes. METHODS: We performed a systematic review and meta-analysis of clinical trials, cohorts, case series, and registry-based studies with the aim to assess (1) the pooled mortality rate of CVST, TTS-associated CVST, and TTS and (2) the pooled proportion of patients with CVST among patients with any thrombotic event and TTS. Secondary outcomes comprised clinical characteristics of patients with postvaccination thrombotic event. This meta-analysis is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology proposal. RESULTS: Sixty-nine studies were included in the qualitative analysis comprising 370 patients with CVST out of 4,182 patients with any thrombotic event associated with SARS-CoV-2 vector-based vaccine administration. Twenty-three studies were included further in quantitative meta-analysis. Among TTS cases, the pooled proportion of CVST was 51% (95% confidence interval [CI] 36%-66%; I 2 = 61%). TTS was independently associated with a higher likelihood of CVST when compared to patients without TTS with thrombotic events after vaccination (odds ratio 13.8; 95% CI 2.0-97.3; I 2 = 78%). The pooled mortality rates of TTS and TTS-associated CVST were 28% (95% CI 21%-36%) and 38% (95% CI 27%-49%), respectively. Thrombotic complications developed within 2 weeks of exposure to vector-based SARS-CoV-2 vaccines (mean interval 10 days; 95% CI 8-12) and affected predominantly women (69%; 95% CI 60%-77%) under age 45, even in the absence of prothrombotic risk factors. DISCUSSION: Approximately half of patients with TTS present with CVST; almost one-third of patients with TTS do not survive. Further research is required to identify independent predictors of TTS following adenovirus vector-based vaccination. REGISTRATION INFORMATION: The prespecified study protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (CRD42021250709).

5.
Lancet Reg Health Eur ; 13: 100294, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1587066

ABSTRACT

In the summer of 2021, European governments removed most NPIs after experiencing prolonged second and third waves of the COVID-19 pandemic. Most countries failed to achieve immunization rates high enough to avoid resurgence of the virus. Public health strategies for autumn and winter 2021 have ranged from countries aiming at low incidence by re-introducing NPIs to accepting high incidence levels. However, such high incidence strategies almost certainly lead to the very consequences that they seek to avoid: restrictions that harm people and economies. At high incidence, the important pandemic containment measure 'test-trace-isolate-support' becomes inefficient. At that point, the spread of SARS-CoV-2 and its numerous harmful consequences can likely only be controlled through restrictions. We argue that all European countries need to pursue a low incidence strategy in a coordinated manner. Such an endeavour can only be successful if it is built on open communication and trust.

6.
Viruses ; 14(1)2021 Dec 24.
Article in English | MEDLINE | ID: covidwho-1580409

ABSTRACT

Health-Care-Workers (HCWs) are considered at high risk for SARS-CoV-2 infection. We sought to compare rates and severity of Coronavirus disease 2019 (COVID-19) among vaccinated and unvaccinated HCWs conducting a retrospective cohort study in two tertiary Academic Hospitals, namely Laiko and Attikon, in Athens, Greece. Vaccinated by BNT162b2 Pfizer-BioNTech COVID-19 mRNA vaccine and unvaccinated HCWs were included and data were collected between 1 January 2021 and 15 September 2021. Overall, 2921 of 3219 HCWs without a history of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection were fully vaccinated during the study period (90.7% at each Hospital). Demographic characteristics were comparable between 102/2921 (3.5%) vaccinated and 88/298 (29.5%) unvaccinated HCWs with COVID-19, although age and occupation differed significantly. None were in need of hospital admission in the vaccinated Group, whereas in the unvaccinated Group 4/88 (4.5%) were hospitalized and one (1.1%) died. Multivariable logistic regression analysis revealed that lack of vaccination was an independent risk factor for COVID-19 with an odds ratio 11.54 (95% CI: 10.75-12.40). Vaccination hesitancy among HCWs resulted to highly increased COVID-19 rates; almost one in three unvaccinated HCWs was SARS-CoV-2 infected during the 9-month period. The absolute need of vaccination of HCWs, including boosting dose, is highlighted. Evidence should be used appropriately to overcome any hesitancy.

7.
Scand J Public Health ; : 14034948211059968, 2021 Dec 13.
Article in English | MEDLINE | ID: covidwho-1571694

ABSTRACT

AIMS: While healthcare services have been expanding capacity during the COVID-19 pandemic, quality of care under increasing patient loads has received less attention. We examined in-hospital mortality of intubated COVID-19 patients in Greece, in relation to total intubated patient load, intensive care unit (ICU) availability and hospital region. METHODS: Anonymized surveillance data were analyzed from all intubated COVID-19 patients in Greece between 1 September 2020 and 6 May 2021. Poisson regression was used to estimate the hazard of dying as a function of fixed and time-varying covariates. RESULTS: Mortality was significantly increased above 400 patients, with an adjusted hazard ratio of 1.25 (95% confidence interval (CI): 1.03-1.51), rising progressively up to 1.57 (95% CI: 1.22-2.02) for 800+ patients. Hospitalization outside an ICU or away from the capital region of Attica were also independently associated with significantly increased mortality. CONCLUSIONS: Our results indicate that in-hospital mortality of severely ill COVID-19 patients is adversely affected by high patient load even without exceeding capacity, as well as by regional disparities. This highlights the need for more substantial strengthening of healthcare services, focusing on equity and quality of care besides just expanding capacity.

8.
Clin Microbiol Infect ; 2021 Nov 22.
Article in English | MEDLINE | ID: covidwho-1525742

ABSTRACT

SCOPE: In January 2021, the ESCMID Executive Committee (EC) decided to launch a new initiative to develop ESCMID guidelines on several COVID19-related issues, including treatment of COVID-19. METHODS: An ESCMID COVID-19 guidelines task force was established by the ESCMID Executive Committee. A small group was established, half appointed by the chair, and the remaining selected with an open call. Each panel met virtually once a week. For all decisions, a simple majority vote was used. A long list of clinical questions using the PICO (population, intervention, comparison, outcome) format was developed at the beginning of the process. For each PICO, two panel members performed a literature search with a third panelist involved in case of inconsistent results. Voting was based on the GRADE approach. QUESTIONS ADDRESSED BY THE GUIDELINE AND RECOMMENDATIONS: A synthesis of the available evidence and recommendations are provided for each of the 15 PICOs, which cover use of hydroxychloroquine, bamlanivimab alone or in combination with etesevimab, casirivimab combined with imdevimab, ivermectin, azithromycin and empirical antibiotics, colchicine, corticosteroids, convalescent plasma, favipiravir, remdesivir, tocilizumab, and interferon ß-1a, as well as the utility of antifungal prophylaxis and enoxaparin. In general, the panel recommended against the use of hydroxychloroquine, ivermectin, azithromycin, colchicine, and interferon ß-1a. Conditional recommendations were given for the use of monoclonal antibodies in high-risk outpatients with mild-moderate COVID-19, and remdesivir. There was insufficient evidence to make a recommendation for use of favipiravir and antifungal prophylaxis, and it was recommended that antibiotics should not be routinely prescribed in patients with COVID-19 unless bacterial coinfection or secondary infection is suspected or confirmed. Tocilizumab and corticosteroids was recommended for treatment of severe COVID-19 but not in outpatients with non-severe COVID-19.

10.
Infect Dis (Lond) ; : 1-10, 2021 Nov 07.
Article in English | MEDLINE | ID: covidwho-1505665

ABSTRACT

BACKGROUND: Understanding the factors that affect the transmissibility of SARS-CoV-2 remains important to keep transmission low and maximize the health benefits of vaccination. We assessed the factors associated with the transmissibility of SARS-CoV-2 based on contact tracing data. METHODS: From 1 October to 9 December 2020, 29,385 laboratory-confirmed SARS-CoV-2 cases (index cases, i.e. the first identified laboratory-confirmed cases or with the earliest symptom onset in a setting) and 64,608 traced contacts were identified in Greece. We assessed the prevalence of symptoms in cases, calculated secondary attack rates and assessed factors associated with infectivity and susceptibility to infection. RESULTS: There were 11,232 contacts secondarily infected (secondary attack rate: 17.4%, 95% CI:17.0-17.8). Contacts aged 0-11 and 12-17 years were less susceptible to infection than adults 65 years or older (odds ratio (OR) [95% CI]: 0.28 [0.26-0.32] and 0.44 [0.40-0.49], respectively). Index cases aged 65 years or older were more likely to infect their contacts than other adults or children/adolescents. The odds of infection [95% CI] were higher in contacts exposed within the household (1.71 [1.59-1.85] vs. other) and in cases with cough (1.17 [1.11-1.25] vs. no cough). There was an interaction between the age of the index and the age of the contact with contacts 65 years or older having a higher probability of infection when exposed to cases of similar age than to children. CONCLUSIONS: Our findings highlight the role of age and age mixing in infectivity and susceptibility to SARS-CoV-2 infection. Precautions are necessary for individuals 65 or older as they have higher infectivity and susceptibility in contact with their peers.

11.
J Med Virol ; 2021 Oct 28.
Article in English | MEDLINE | ID: covidwho-1487497

ABSTRACT

Accumulating data has shown a contribution of the renin-angiotensin system in COVID-19 pathogenesis. The role of angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism as a risk factor in developing COVID-19 disease comes from epidemiological data and is controversially discussed. We conducted a retrospective case-control study and assessed the impact of ACE I/D genotype in COVID-19 disease prevalence and severity. In 81 COVID-19 patients explicitly characterized and 316 controls, recruited during the first wave of COVID-19 pandemic, ACE I/D genotype, and ACE activity were determined. A generalized linear model was used and Poisson regression analysis estimated the risk ratios (RRs) of alleles and genotypes for disease severity. DD patients had almost 2.0-fold increased risk (RR: 1.886, confidence limit [CL] 95%: 1.266-2.810, p = 0.0018) of developing a more severe disease when contrasted to ID and II individuals, as did D allele carriers compared to I carriers (RR: 1.372; CL 95%: 1.051-1.791; p = 0.0201). ACE activity (expressed as arbitrary units, AU/L) was lower in patients (3.62 ± 0.26) than in controls (4.65 ± 0.13) (p < 0.0001), and this reduction was observed mainly among DD patients compared to DD controls (3.97 ± 0.29 vs. 5.38 ± 0.21; p = 0.0014). Our results demonstrate that ACE DD genotype may predispose to COVID-19 increased disease severity via a mechanism associated, at least in part, with the significant fall in their ACE activity. Our findings suggest a more complex pattern of synergy between this polymorphism and ACE activity in COVID-19 patients compared to healthy individuals and set the grounds for large-scale studies assessing ACE genotype-based optimized therapies with ACE inhibitors and angiotensin receptor blockers.

12.
Neurology ; 97(21): e2136-e2147, 2021 11 23.
Article in English | MEDLINE | ID: covidwho-1456030

ABSTRACT

BACKGROUND AND OBJECTIVES: There is accumulating evidence supporting an association between the thrombosis and thrombocytopenia syndrome (TTS) and adenovirus vector-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Yet TTS and TTS-associated cerebral venous sinus thrombosis (CVST) remain poorly characterized. We aim to systematically evaluate the proportion of CVST among TTS cases and assess its characteristics and outcomes. METHODS: We performed a systematic review and meta-analysis of clinical trials, cohorts, case series, and registry-based studies with the aim to assess (1) the pooled mortality rate of CVST, TTS-associated CVST, and TTS and (2) the pooled proportion of patients with CVST among patients with any thrombotic event and TTS. Secondary outcomes comprised clinical characteristics of patients with postvaccination thrombotic event. This meta-analysis is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology proposal. RESULTS: Sixty-nine studies were included in the qualitative analysis comprising 370 patients with CVST out of 4,182 patients with any thrombotic event associated with SARS-CoV-2 vector-based vaccine administration. Twenty-three studies were included further in quantitative meta-analysis. Among TTS cases, the pooled proportion of CVST was 51% (95% confidence interval [CI] 36%-66%; I 2 = 61%). TTS was independently associated with a higher likelihood of CVST when compared to patients without TTS with thrombotic events after vaccination (odds ratio 13.8; 95% CI 2.0-97.3; I 2 = 78%). The pooled mortality rates of TTS and TTS-associated CVST were 28% (95% CI 21%-36%) and 38% (95% CI 27%-49%), respectively. Thrombotic complications developed within 2 weeks of exposure to vector-based SARS-CoV-2 vaccines (mean interval 10 days; 95% CI 8-12) and affected predominantly women (69%; 95% CI 60%-77%) under age 45, even in the absence of prothrombotic risk factors. DISCUSSION: Approximately half of patients with TTS present with CVST; almost one-third of patients with TTS do not survive. Further research is required to identify independent predictors of TTS following adenovirus vector-based vaccination. REGISTRATION INFORMATION: The prespecified study protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (CRD42021250709).

13.
Microbiol Spectr ; 9(2): e0126021, 2021 10 31.
Article in English | MEDLINE | ID: covidwho-1455683

ABSTRACT

Severe COVID-19 pneumonia has been associated with the development of intense inflammatory responses during the course of infections with SARS-CoV-2. Given that human endogenous retroviruses (HERVs) are known to be activated during and participate in inflammatory processes, we examined whether HERV dysregulation signatures are present in COVID-19 patients. By comparing transcriptomes of bronchoalveolar lavage fluid (BALF) of COVID-19 patients and healthy controls, and peripheral blood monocytes (PBMCs) from patients and controls, we have shown that HERVs are intensely dysregulated in BALF of COVID-19 patients compared to those in BALF of healthy control patients but not in PBMCs. In particular, upregulation in the expression of specific HERV families was detected in BALF samples of COVID-19 patients, with HERV-FRD being the most highly upregulated family among the families analyzed. In addition, we compared the expression of HERVs in human bronchial epithelial cells (HBECs) without and after senescence induction in an oncogene-induced senescence model in order to quantitatively measure changes in the expression of HERVs in bronchial cells during the process of cellular senescence. This apparent difference of HERV dysregulation between PBMCs and BALF warrants further studies in the involvement of HERVs in inflammatory pathogenetic mechanisms as well as exploration of HERVs as potential biomarkers for disease progression. Furthermore, the increase in the expression of HERVs in senescent HBECs in comparison to that in noninduced HBECs provides a potential link for increased COVID-19 severity and mortality in aged populations. IMPORTANCE SARS-CoV-2 emerged in late 2019 in China, causing a global pandemic. Severe COVID-19 is characterized by intensive inflammatory responses, and older age is an important risk factor for unfavorable outcomes. HERVs are remnants of ancient infections whose expression is upregulated in multiple conditions, including cancer and inflammation, and their expression is increased with increasing age. The significance of this work is that we were able to recognize dysregulated expression of endogenous retroviral elements in BALF samples but not in PBMCs of COVID-19 patients. At the same time, we were able to identify upregulated expression of multiple HERV families in senescence-induced HBECs in comparison to that in noninduced HBECs, a fact that could possibly explain the differences in disease severity among age groups. These results indicate that HERV expression might play a pathophysiological role in local inflammatory pathways in lungs afflicted by SARS-CoV-2 and their expression could be a potential therapeutic target.


Subject(s)
Bronchioles/virology , Bronchoalveolar Lavage Fluid/virology , COVID-19/pathology , Endogenous Retroviruses/growth & development , Respiratory Mucosa/virology , Bronchioles/cytology , Endogenous Retroviruses/isolation & purification , Epithelial Cells/virology , Humans , Inflammation/virology , Leukocytes, Mononuclear/virology , Respiratory Mucosa/cytology , SARS-CoV-2 , Transcriptome/genetics , Up-Regulation
14.
Vaccines (Basel) ; 9(9)2021 Sep 13.
Article in English | MEDLINE | ID: covidwho-1438752

ABSTRACT

BNT162b2 has proven to be highly effective, but there is a paucity of data regarding immunogenicity factors and comparison between response to vaccination and natural infection. This study included 871 vaccinated healthcare workers (HCW) and 181 patients with natural infection. Immunogenicity was assessed by measuring anti-SARS-CoV-2 against the RBD domain of the spike protein (anti-RBD). Samples were collected 1-2 weeks after vaccination or 15-59 days post-onset of symptoms. Post-vaccine anti-RBD concentrations were associated with age, gender, vaccination side-effects (VSE) and prior infection (Pr-CoV). Anti-RBD median levels (95%CI) were lower by 2466 (651-5583), 6228 (3254-9203) and 7651 (4479-10,823) AU/mL in 35-44, 45-54, 55-70 yrs, respectively, compared with the 18-34 yrs group. In females, the median levels were higher by 2823 (859-4787), 5024 (3122-6926) in individuals with VSE, and 9971 (5158-14,783) AU/mL in HCWs with Pr-CoV. The ratio of anti-RBD in vaccinated individuals versus those with natural infection varied from 1.0 to 19.4. The high immunogenicity of BNT162b2 is verified, although its sustainability has yet to be elucidated. The use of comparative data from natural infection serological panels, expressing the clinical heterogeneity of natural infection, may facilitate early decisions for candidate vaccines to be evaluated in clinical trials.

15.
Nature ; 599(7883): 108-113, 2021 11.
Article in English | MEDLINE | ID: covidwho-1434121

ABSTRACT

Throughout the coronavirus disease 2019 (COVID-19) pandemic, countries have relied on a variety of ad hoc border control protocols to allow for non-essential travel while safeguarding public health, from quarantining all travellers to restricting entry from select nations on the basis of population-level epidemiological metrics such as cases, deaths or testing positivity rates1,2. Here we report the design and performance of a reinforcement learning system, nicknamed Eva. In the summer of 2020, Eva was deployed across all Greek borders to limit the influx of asymptomatic travellers infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and to inform border policies through real-time estimates of COVID-19 prevalence. In contrast to country-wide protocols, Eva allocated Greece's limited testing resources on the basis of incoming travellers' demographic information and testing results from previous travellers. By comparing Eva's performance against modelled counterfactual scenarios, we show that Eva identified 1.85 times as many asymptomatic, infected travellers as random surveillance testing, with up to 2-4 times as many during peak travel, and 1.25-1.45 times as many asymptomatic, infected travellers as testing policies that utilize only epidemiological metrics. We demonstrate that this latter benefit arises, at least partially, because population-level epidemiological metrics had limited predictive value for the actual prevalence of SARS-CoV-2 among asymptomatic travellers and exhibited strong country-specific idiosyncrasies in the summer of 2020. Our results raise serious concerns on the effectiveness of country-agnostic internationally proposed border control policies3 that are based on population-level epidemiological metrics. Instead, our work represents a successful example of the potential of reinforcement learning and real-time data for safeguarding public health.


Subject(s)
COVID-19/diagnosis , COVID-19/prevention & control , Carrier State/diagnosis , Carrier State/prevention & control , Machine Learning , Travel Medicine , Travel , COVID-19/epidemiology , COVID-19/transmission , Carrier State/epidemiology , Carrier State/transmission , Greece , Humans , Prevalence , Public Health
16.
Viruses ; 13(9)2021 09 15.
Article in English | MEDLINE | ID: covidwho-1411088

ABSTRACT

COVID-19 is an ongoing pandemic with high morbidity and mortality. Despite meticulous research, only dexamethasone has shown consistent mortality reduction. Convalescent plasma (CP) infusion might also develop into a safe and effective treatment modality on the basis of recent studies and meta-analyses; however, little is known regarding the kinetics of antibodies in CP recipients. To evaluate the kinetics, we followed 31 CP recipients longitudinally enrolled at a median of 3 days post symptom onset for changes in binding and neutralizing antibody titers and viral loads. Antibodies against the complete trimeric Spike protein and the receptor-binding domain (Spike-RBD), as well as against the complete Nucleocapsid protein and the RNA binding domain (N-RBD) were determined at baseline and weekly following CP infusion. Neutralizing antibody (pseudotype NAb) titers were determined at the same time points. Viral loads were determined semi-quantitatively by SARS-CoV-2 PCR. Patients with low humoral responses at entry showed a robust increase of antibodies to all SARS-CoV-2 proteins and Nab, reaching peak levels within 2 weeks. The rapid increase in binding and neutralizing antibodies was paralleled by a concomitant clearance of the virus within the same timeframe. Patients with high humoral responses at entry demonstrated low or no further increases; however, virus clearance followed the same trajectory as in patients with low antibody response at baseline. Together, the sequential immunological and virological analysis of this well-defined cohort of patients early in infection shows the presence of high levels of binding and neutralizing antibodies and potent clearance of the virus.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/virology , Nucleocapsid/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Viral Load , Aged , Aged, 80 and over , Antibody Formation/immunology , COVID-19/therapy , Female , Host-Pathogen Interactions , Humans , Immunization, Passive , Kinetics , Male , Middle Aged
17.
Sci Total Environ ; 804: 150151, 2022 Jan 15.
Article in English | MEDLINE | ID: covidwho-1401851

ABSTRACT

We measured SARS-CoV-2 RNA load in raw wastewater in Attica, Greece, by RT-qPCR for the environmental surveillance of COVID-19 for 6 months. The lag between RNA load and pandemic indicators (COVID-19 hospital and intensive care unit (ICU) admissions) was calculated using a grid search. Our results showed that RNA load in raw wastewater is a leading indicator of positive COVID-19 cases, new hospitalization and admission into ICUs by 5, 8 and 9 days, respectively. Modelling techniques based on distributed/fixed lag modelling, linear regression and artificial neural networks were utilized to build relationships between SARS-CoV-2 RNA load in wastewater and pandemic health indicators. SARS-CoV-2 mutation analysis in wastewater during the third pandemic wave revealed that the alpha-variant was dominant. Our results demonstrate that clinical and environmental surveillance data can be combined to create robust models to study the on-going COVID-19 infection dynamics and provide an early warning for increased hospital admissions.


Subject(s)
COVID-19 , SARS-CoV-2 , Hospitalization , Humans , Intensive Care Units , RNA, Viral , Waste Water , Wastewater-Based Epidemiological Monitoring
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