BMC Infectious Diseases

Backgroundcontroversy has arisen in the scientific community on whether the use of renin angiotensin system (RAS) inhibitors in the context of COVID-19 would be of benefit or harmful. A meta-analysis of eligible studies comparing the occurrence of severe and fatal COVID-19 in infected patients who were under treatment with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) vs no treatment or other antihypertensives was conducted. MethodsPubMed, Google Scholar, the Cochrane Library, MedRxiv and BioRxiv were searched for relevant studies. Fixed-effect models or random-effect models were used depending on the heterogeneity between estimates. Resultsa total of fifteen studies with 21,614 patients were included. The use of RAS inhibitors was associated with a non-significant 20% decreased risk of the composite outcome (death, admission to intensive care unit, mechanical ventilation requirement or progression to severe or critical pneumonia): RR 0.81 (95%CI: 0.631.04), p=0.10, I2=82%. In a subgroup analysis that included hypertensive subjects only, ACEI/ARB were associated with a 27% significant decrease in the risk of the composite outcome (RR 0.73 (95%CI: 0.56 0.96), p=0.02, I2=65%). Conclusionthe results of this pooled analysis suggest that the use of ACEI/ARB does not worsen the prognosis, and could even be protective in hypertensive subjects. Patients should continue these drugs during their COVID-19 illness.

Fevers have been used as marker of disease state for hundreds of years and are frequently used to screen for infectious diseases during infectious disease outbreaks. However, body temperature and fevers have been shown to vary over the course of a day and across individuals by age, sex and other characteristics. The objective of this paper is to describe the individual variation in diurnal temperature patterns during episodes of febrile activity using a database of millions of recorded temperatures across the United States. We then model the probability of recording a fever during a single reading at given time for individuals who are experiencing a febrile episode. We find a wide variation in body temperatures over the course of a day and across individual characteristics. Similarly, the likelihood of recording a fever may vary widely by the time of day when the reading is taken and by an individuals age or sex. These results suggest diurnal temperature variation and demographics should be considered when using body temperature to screen for disease, especially for diseases that are contagious.

ABSTRACT BACKGROUND: Currently, there is no proven effective therapy nor vaccine for the treatment of SARS-CoV-2. Evidence regarding the potential benefit of early administration of hydroxychloroquine (HCQ) therapy in symptomatic patients with Coronavirus Disease (COVID-19) is not clear. METHODS: This observational prospective cohort study took place in 238 ambulatory fever clinics in Saudi Arabia, which followed the Ministry of Health (MOH) COVID-19 treatment guideline. This guideline included multiple treatment options for COVID-19 based on the best available evidence at the time, among which was Hydroxychloroquine (HCQ). Patients with confirmed COVD-19 (by reverse transcriptase polymerase chain reaction (PCR) test) who presented to these clinics with mild to moderate symptoms during the period from 5-26 June 2020 were included in this study. Our study looked at those who received HCQ-based therapy along with supportive care (SC) and compared them to patients who received SC alone. The primary outcome was hospital admission within 28-days of presentation. The secondary outcome was a composite of intensive care admission (ICU) and/or mortality during the follow-up period. Outcome data were assessed through a follow-up telephonic questionnaire at day 28 and were further verified with national hospitalisation and mortality registries. Multiple logistic regression model was used to control for prespecified confounders. RESULTS: Of the 7,892 symptomatic PCR-confirmed COVID-19 patients who visited the ambulatory fever clinics during the study period, 5,541 had verified clinical outcomes at day 28 (1,817 patients in the HCQ group vs 3,724 in the SC group). At baseline, patients who received HCQ therapy were more likely to be males who did not have hypertension or chronic lung disease compared to the SC group. No major differences were noted regarding other comorbid conditions. All patients were presenting with active complaints; however, the HCQ groups had higher rates of symptoms compared to the SC group (fever: 84% vs 66.3, headache: 49.8 vs 37.4, cough: 44.5 vs 35.6, respectively). Early HCQ-based therapy was associated with a lower hospital admission within 28-days compared to SC alone (9.4% compared to 16.6%, RRR 43%, p-value <0.001). The composite outcome of ICU admission and/or mortality at 28-days was also lower in the HCQ group compared to the SC (1.2% compared to 2.6%, RRR 54%, p-value 0.001). Adjusting for age, gender, and major comorbid conditions, a multivariate logistic regression model showed a decrease in the odds of hospitalisation in patients who received HCQ compared to SC alone (adjusted OR 0.57 [95% CI 0.47-0.69], p-value <0.001). The composite outcome of ICU admission and/or mortality was also lower for the HCQ group compared to the SC group controlling for potential confounders (adjusted OR 0.55 [95% CI 0.34-0.91], p-value 0.019). CONCLUSION: Early intervention with HCQ-based therapy in patients with mild to moderate symptoms at presentation is associated with lower adverse clinical outcomes among COVID-19 patients, including hospital admissions, ICU admission, and/or death.

BackgroundMost patients infected by SARS-CoV-2 have favourable outcomes, however some develop severe disease which may progress to acute respiratory distress syndrome, multi-organ failure, and death. Markers that could predict patients at risk of poor outcomes would be extremely useful clinically. Evidence has emerged that low lymphocyte count is associated with increased disease severity. MethodsWe performed a systematic review and meta-analysis to assess the association between lymphocyte count and severity of SARS-CoV-2 associated clinical disease. ResultsSeven papers were included in the meta-analysis. These papers included data from 2083 patients, 25% (n=521) with severe SAR-CoV-2 disease and 75% (n=1562) with non-severe SAR-CoV-2 disease. Heterogenicity was seen in the definition of severe disease. Metanalysis produced metamedians of 1x109/L (95% CI 1-1.1) and 0.7x109/L (95% CI 0.63-0.8) lymphocytes for patients with non-severe and severe disease respectively (p-value of p=0.006 Wilcoxon test). Calculation of metamedians from the two papers classifying severe disease according to death alone gave 1.1 1x109/L lymphocytes (95% CI 1.0-1.1) for survivors (n=163) and 0.63 1x109/L lymphocytes (95% CI 0.60-0.63) for non-survivors (n=253) of SAR-CoV-2 disease. ConclusionsLower lymphocyte counts are significantly associated with more severe disease in patients with SARS-CoV-2 infection. Lymphocytopenia may therefore be useful laboratory measure to allow prognostication of patients presenting with SARS-CoV-2 infection.

BackgroundThe burden of COVID-19 in Canada is unequally distributed geographically, with the largest number of cases and fatalities recorded in Quebec and Ontario while other provinces experienced limited outbreaks. To date, however, no study has assessed how provincial epidemics have unfolded in a comparative perspective. This is essential to calibrate projections of the future course of the epidemic and plan health care resources for the second wave of infections. MethodsUsing newly released individual-level data collected by the Public Health Agency of Canada, we assess COVID-19-related morbidity and mortality across age and gender groups at the provincial level through a combination of demographic and survival analyses. ResultsQuebec has the highest absolute and per capita number of COVID-19 confirmed positive cases, hospitalizations and fatalities in all age groups. In each province, a higher number of women than men test positive for the disease, especially above age 80. Yet consistently across age groups, infected men are more likely to be hospitalized and enter intensive care than women do. These gender differences in hospitalisation rates account for the higher case fatality risk due to COVID-19 among men compared to women. InterpretationAlthough health care capacity across provinces has been sufficient to treat severe cases, we find that the main factor accounting for gender differences in COVID-19-related mortality is the need for hospitalization and intensive care, especially above age 80. This suggests a selection effect of severe cases requiring to be treated in a hospital setting that needs to be further investigated.

BackgroundThe transmissibility of SARS-CoV-2 determines both the ability of the virus to invade a population and the strength of intervention that would be required to contain or eliminate the spread of infection. The basic reproduction number, R0, provides a quantitative measure of the transmission potential of a pathogen. ObjectiveConduct a scoping review of the available literature providing estimates of R0 for SARS-CoV-2, provide an overview of the drivers of variation in R0 estimates and the considerations taken in the calculation of the parameter. DesignScoping review of available literature between the 01 December 2019 and 07 May 2020. Data sourcesBoth peer-reviewed and pre-print articles were searched for on PubMed, Google Scholar, MedRxiv and BioRxiv. Selection criteriaStudies were selected for review if (i) the estimation of R0 for SARS-CoV-2 represented either the initial stages of the outbreak or the initial stages of the outbreak prior to the onset of widespread population restriction ("lockdown"), (ii) the exact dates of the study period were provided and (iii) the study provided primary estimates of R0. ResultsA total of 20 R0 for SARS-CoV-2 estimates were extracted from 15 studies. There was substantial variation in the estimates reported. Estimates derived from mathematical models fell within a wider range of 1.94-6.94 than statistical models which fell between the range of 2.2 to 4.4. Several studies made assumptions about the length of the infectious period which ranged from 5.8-20 days and the serial interval which ranged from 4.41-14 days. For a given set of parameters a longer duration of infectiousness or a longer serial interval equates to a higher R0. Several studies took measures to minimise bias in early case reporting, to account for the potential occurrence of super-spreading events, and to account for early sub-exponential epidemic growth. ConclusionsThe variation in reported estimates of R0 reflects the complex nature of the parameter itself, including the context (i.e. social/spatial structure), the methodology used to estimate the parameter, and model assumptions. R0 is a fundamental parameter in the study of infectious disease dynamics, however it provides limited practical applicability outside of the context in which it was estimated, and should be calculated and interpreted with this in mind. STRENGTHS AND LIMITATIONS OF THE SCOPING REVIEWO_LIThis study provides an overview of basic reproduction number estimates for SARS-CoV-2 across a range of settings, a fundamental parameter in gauging the transmissibility of an emerging infectious disease. C_LIO_LIThe key drivers of variation in R0 estimates and considerations in the calculation of the parameter highlighted across the reviewed studies are discussed. C_LIO_LIThis evidence may be used to help inform modelling studies and intervention strategies. C_LIO_LIGiven the need for rapid dissemination of information on a newly emerging infectious disease, several of the reviewed papers were in the pre-print phase yet to be peer-reviewed. C_LI

BackgroundTo date, accessible diagnostic tools to identify whether a patients pneumonia is a bacterial, or viral infection, are not accurate or timely enough to prevent preemptive antibiotic administration. Relying on single biomarkers or clinical presentations has been insufficient. We aimed to incorporate a wide range of novel biomarkers and clinical presentations in a multivariable model and validate its capacity to differentiate cases of bacterial and viral pneumonia. MethodsData from 457 children aged 2-59 months, admitted to Kilifi County Referral Hospital, Kenya, with bacterial (n = 229) and viral (n = 228) infections, were used to develop and validate a predictive multivariable Poisson regression model to differentiate pneumonia etiology. The Receiver Operating Characteristic curve was used to assess biomarker performance and validate the model internally. ResultsSixty-three percent (63%) of the children presented with severe pneumonia. 72% with viral pneumonia had severe pneumonia, compared to 54% with bacterial pneumonia who had severe pneumonia. In crude analyses, chest-wall indrawing, cough, convulsions, crackles, angiotensinogen, and Serpin Family A Member 1 were significantly associated with pneumonia etiology, controlling for age. However, only chest-wall indrawing remained significant in multivariable analyses after controlling for age. The model demonstrated fair, but inadequate, discrimination, with an Area Under the Curve of 0.61. ConclusionAmong the children admitted to hospital with WHO defined pneumonia, a wide range of biomarkers and clinical presentations still failed to distinguish bacterial from viral pneumonia.

BackgroundCare home residents are at high risk of severe outcomes following respiratory infection due to age, co-morbidities, and close contact with staff and other residents. Frequent staff testing could potentially reduce respiratory infection cases in residents, but evidence is limited. This study uses historical COVID-19 data in England to assess the impact of varying staff testing rates under different transmission scenarios to inform response during future pandemics. MethodsWe developed a compartmental model of SARS-CoV-2 transmission in England, with three population strata: general population, care home staff, and residents. The model was calibrated using prevalence data from January 2021 to March 2022 and testing rates from the VIVALDI Study (ISRCTN14447421). We conducted a scenario analysis projecting resident cases and deaths over 12 months under varying staff testing frequencies (monthly, twice-monthly, weekly, twice-weekly, daily) assuming a new dominant strain. We also explored the impact of testing when combined with a hypothetical low-cost highly-effective public health and social measures. FindingsStaff testing alone has little impact on reducing cases and deaths in the resident population. Daily testing could avert only 3.8% (95%UI: 3.1-4.4%) cases and 3.5% (95%UI: 2.3-4.4%) deaths compared to a baseline testing of less than one test per month. When combined with public health and social measures, however, the effect is large. Daily staff testing, combined with public health and social measures, can reduce resident cases by 54% (95%UI: 50-58%) and deaths by 50% (95%UI: 26-59%). Additionally, if testing frequency is reduced but there is still a public health and social measure, the effect size decreases, however there are potential cost savings ({pound}0.7 to {pound}3.4 million). InterpretationIncreasing staff testing alone is insufficient to significantly reduce SARS-CoV-2 cases and deaths in care home residents. However, combining testing with some form of a public health and social measure aimed at reducing transmission among residents, is epidemiologically effective and cost-effective in most scenarios and possibly cost saving.

BackgroundThe COVID-19 pandemic has affected the entire world, but there are wide variations in prevalence and mortality across nations. Genetic variants which influence behavioural or immune responses to pathogens, selected for by pathogen pressure, may influence this variability. Two relevant polymorphisms in this context are the s allele of the serotonin transporter promoter (5-HTTLPR) and the G allele of the interleukin-6 gene (IL-6 rs1800795). MethodsThe frequencies of the 5-HTTLPR s allele and IL-6 rs1800795 G allele were obtained from published data. The correlations between these allele frequencies and the prevalence and mortality rates of COVID-19 were examined across 44 nations. ResultsThe IL-6 rs1800795 G allele was negatively correlated with COVID-19 prevalence ({rho} = -0.466, p < 0.01) and mortality ({rho} = -0.591, p<0.001) across nations. The 5-HTTLPR s allele was negatively correlated with COVID-19 mortality rates ({rho} = -0.437, p = 0.023). ConclusionsThese results suggest that a significant relationship exists between genetic variants that influence behavioural and immune responses to pathogens and indices of the impact of COVID-19 across nations. Further investigation of these variants and their correlates may permit the development of better preventive or therapeutic strategies in the management of the COVID-19 pandemic.

IMPORTANCECoronavirus disease 2019 (COVID-19) is a global pandemic associated with high mortality and effective treatment to prevent clinical deterioration to severe pneumonia has not yet been well clarified. OBJECTIVETo investigate the role of several adjuvant treatments in preventing severe pneumonia in patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTSMulticenter, retrospective cohort study of 564 consecutively hospitalized patients with confirmed COVID-19 at Third Xiangya Hospital of Central South University, Changsha Public Health Treatment Center, First Hospital of Yueyang, Junshan Peoples Hospital of Yueyang, Central Hospital of Shaoyang, Central Hospital of Xiangtan, Second Hospital of Changde, Central Hospital of Loudi, and First Affiliated Hospital of University of South China in Hunan province from January 17, 2020 to February 28, 2020; The final date of follow-up was March 15, 2020. EXPOSURESNonspecific antivirals (arbidol, lopinavir/ritonavir, and interferon ), antihypertensives, and chloroquine. MAIN OUTCOMES AND MEASURESThe development of severe COVID-19 pneumonia; Demographic, epidemiological, clinical, laboratory, radiological, and treatment data were collected and analyzed. RESULTSOf 564 patients, the median age was 47 years (interquartile range, 36-58 years), and 284 (50.4%) patients were men. Sixty-nine patients (12.2%) developed severe pneumonia. Patients who developed severe pneumonia were older (median age of 59 and 45 years, respectively), and more patients had comorbidities including hypertension (30.4% and 12.3%, respectively), diabetes (17.4% and 6.7%, respectively), and cardiovascular disease (8.7% and 3.2%, respectively) and presented with fever (84.1% and 60.4%, respectively) and shortness of breath (10.1% and 3.8%, respectively) compared with those who did not. Nonspecific antiviral therapy did not prevent clinical progression to severe pneumonia, although fewer hypertensive patients on angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers (ACEI/ARB) therapy developed severe pneumonia in contrast with those on non-ACEI/ARB antihypertensive therapy (1 of 16 [6.3%] patients and 16 of 49 [32.7%] patients, respectively [difference, 26.4%; 95% CI, 1.5% to 41.3%]). Multivariate logistic regression analysis showed that hypertension without receiving ACEI/ARB therapy was an independent risk factor (odds ratio [OR], 2.07; 95% CI, 1.07 to 4.00) for developing severe pneumonia irrespective of age. Besides, none of patients treated with chloroquine developed severe pneumonia, though without significance (difference, 12.0%; 95% CI, -3.5% to 30.0%) by propensity score matching. CONCLUSIONS AND RELEVANCEHypertensive patients on ACEI or ARB may be protective from severe pneumonia in COVID-19 and hence these therapies should not be ceased unless there is a strong indication or further epidemiological evidence. Though none of the current antiviral and immunoregulation therapy showed benefit in preventing COVID-19 progression, chloroquine deserved further investigation. KEYPOINTSO_ST_ABSQuestionC_ST_ABSDoes the use of adjuvant therapy reduce progression to severe pneumonia in patients with coronavirus disease 2019 (COVID-19)? FindingsIn this retrospective, observational cohort study involving 564 patients with confirmed COVID-19, hypertension was an independent risk factor for progression to severe pneumonia irrespective of age and those on angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy were less likely to develop severe COVID-19 pneumonia, while nonspecific antivirals or chloroquine did not have significant impact on clinical progression. MeaningHypertensive patients with COVID-19 should not have ACEI or ARB ceased, unless there is a strong indication or further epidemiological evidence, given its potential protective effects.

BackgroundThe novel coronavirus disease 2019 (COVID-19) outbreak presents a significant threat to global health. A better understanding of patient clinical profiles is essential to drive efficient and timely health service strategies. In this study, we aimed to identify risk factors for a higher susceptibility to symptomatic presentation with COVID-19 and a transition to severe disease. MethodsWe analysed data on 2756 patients admitted to Chelsea & Westminster Hospital NHS Foundation Trust between 1st January and 23rd April 2020. We compared differences in characteristics between patients designated positive for COVID-19 and patients designated negative on hospitalisation and derived a multivariable logistic regression model to identify risk factors for predicting risk of symptomatic COVID-19. For patients with COVID-19, we used univariable and multivariable logistic regression to identify risk factors associated with progression to severe disease defined by: 1) admission to the hospitals AICU, 2) the need for mechanical ventilation, 3) in-hospital mortality, and 4) at least one measurement of elevated D-dimer ([&ge;]1,000 g/L) indicative of increased risk of venous thromboembolism. ResultsThe patient population consisted of 1148 COVID-19 positive and 1608 COVID-19 negative patients. Age, sex, self-reported ethnicity, C-reactive protein, white blood cell count, respiratory rate, body temperature, and systolic blood pressure formed the most parsimonious model for predicting risk of symptomatic COVID-19 at hospital admission. Among 1148 patients with COVID-19, 116 (10.1%) were admitted to the AICU, 71 (6.2%) required mechanical ventilation, 368 (32.1%) had at least one record of D-dimer levels [&ge;]1,000 g/L, and 118 patients died. In the multivariable logistic regression, age (OR = 0.953 per 1 year, 95% CI: 0.937-0.968) C-reactive protein (OR = 1.004 per 1 mg/L, 95% CI: 1.002-1.007), and white blood cell counts (OR = 1.059 per 109/L, 95% CI: 1.010-1.111) were found to be associated with admission to the AICU. Age (OR = 0.973 per 1 year, 95% CI: 0.955-0.990), C-reactive protein (OR = 1.003 per 1 mg/L, 95% CI: 1.000-1.006) and sodium (OR = 0.915 per 1 mmol/L, 0.868-0.962) were associated with mechanical ventilation. Age (OR = 1.023 per 1 year, 95% CI: 1.004-1.043), CRP (OR = 1.004 per 1 mg/L, 95% CI: 1.002-1.006), and body temperature (OR = 0.723 per 1{degrees}C, 95% CI: 0.541-0.958) were associated with elevated D-dimer. For mortality, we observed associations with age (OR = 1.060 per 1 year, 95% CI: 1.040-1.082), female sex (OR = 0.442, 95% CI: 0.442, 95% CI: 0.245-0.777), Asian ethnic background (OR = 2.237 vs White ethnic background, 95% CI: 1.111-4.510), C-reactive protein (OR = 1.004 per 1 mg/L, 95% CI: 1.001-1.006), sodium (OR = 1.038 per 1 mmol/L, 95% CI: 1.001-1.006), and respiratory rate (OR = 1.054 per 1 breath/min, 95% CI: 1.024-1.087). ConclusionOur analysis suggests there are several demographic, clinical and laboratory findings associated with a symptomatic presentation of COVID-19. Moreover, significant associations between patient deterioration were found with age, sex and specific blood markers, chiefly C-reactive protein, and could help early identification of patients at risk of poorer prognosis. Further work is required to clarify the extent to which our observations are relevant beyond current settings.

BackgroundEstimating the prevalence of severe or critical illness and case fatality of COVID-19 outbreak in December, 2019 remains a challenge due to biases associated with surveillance, data synthesis and reporting. We aimed to address this limitation in a systematic review and meta-analysis and to examine the clinical, biochemical and radiological risk factors in a meta-regression. MethodsPRISMA guidelines were followed. PubMed, Scopus and Web of Science were searched using pre-specified keywords on March 07, 2020. Peer-reviewed empirical studies examining rates of severe illness, critical illness and case fatality among COVID-19 patients were examined. Numerators and denominators to compute the prevalence rates and risk factors were extracted. Random-effects meta-analyses were performed. Results were corrected for publication bias. Meta-regression analyses examined the moderator effects of potential risk factors. ResultsThe meta-analysis included 29 studies representing 2,090 individuals. Pooled rates of severe illness, critical illness and case fatality among COVID-19 patients were 15%, 5% and 0.8% respectively. Adjusting for potential underreporting and publication bias, increased these estimates to 26%, 16% and 7.4% respectively. Increasing age and elevated LDH consistently predicted severe / critical disease and case fatality. Hypertension; fever and dyspnea at presentation; and elevated CRP predicted increased severity. ConclusionsRisk factors that emerged in our analyses predicting severity and case fatality should inform clinicians to define endophenotypes possessing a greater risk. Estimated case fatality rate of 7.4% after correcting for publication bias underscores the importance of strict adherence to preventive measures, case detection, surveillance and reporting.

PurposeSevere SARS-CoV-2 pneumonia remains incompletely understood. We aimed to summarize current evidence regarding clinical features, laboratory findings, and treatment of severe pneumonia. MethodsOnline databases were searched from December 1, 2019, to April 15, 2020 related to SARS-CoV-2. The titles and abstracts in English or Chinese for articles were screened. Studies containing more than 10 adult patients with severe pneumonia and presenting data on clinical features and laboratory findings were selected and extracted independently by two reviewers. ResultsWe identified a total of 13 articles including one from Italy representing the majority of cases, and the remainder from China. Over the 2,129 severe pneumonia in these 13 articles, the mean ages ranged from 49 to 64 years. Patients typically presented with hypertension as the most common comorbid factor, fever as the most common symptom, and acute respiratory distress syndrome as the most common complication. As compared to non-severe pneumonia, severe pneumonia featured lower counts of lymphocytes, CD8+ and CD4+ T cells, and higher levels of D-dimer, lactate dehydrogenase, IL-6 and IL-10. There is a lack of evidence for using antivirals, and a debate on using corticosteroids in treatment. ConclusionsThis is the first systematic summarization of the aspects of severe pneumonia. Older age, comorbidities, laboratory findings might be the predisposing factors of disease severity. Multicenter- and large population-designed studies, with confounding controlled and long enough to accommodate follow-ups, are urgently required to provide the guidance to disease management.

1.1.1. Background/PurposeWe share our experience in COVID-19 pneumonia management at Saint George Hospital University Medical Center (SGHUMC) in Lebanon. In the absence of a standard of care, early diagnosis and opt-in therapy with Hydroxychloroquine and Azithromycin were offered. 1.2. MethodsWe reviewed records of COVID-19 pneumonia patients from March 16-April 26 2020. Based on NEWS score, we stratified patients as A: low B: medium, and C: high clinical severity and obtained pharmacotherapy data. Chest-CT-severity-score (CTSS) was used. We defined clinical cure as resolution of symptoms and biomarkers and virologic cure as a PCR above 35 cycles(Ct). 1.3. ResultsWe recorded 21 COVID-19 pneumonia patients of whom 19 opted for treatment. Clinical symptoms and laboratory markers at presentation did not significantly correlate with severity. Lower initial viral load significantly correlated with lower levels of clinical and radiological severity (p=0.038). Virologic cure, Ct>35, by day 10, was only 33% in high severity significantly less than categories A and B. We observed 100% clinical cure at day 10 in Category-A, 67% in B, and 33% in C(p<0.05). Patients with the lowest severity had the fastest virologic cure in a mean of 5.8 days from diagnosis, shortest hospitalization and earlier radiological improvement(p<0.005). Ultimately, 18 patients were discharged home in good condition and one remains in the ICU. 1.4. ConclusionViral dynamics matter in COVID-19 pneumonia. An early control of replication may be crucial in averting complications. Early administration of Hydroxychloroquine and Azithromycin potentially explains our 94.7% success rate in treating a fairly complex cohort of COVID-19 pneumonia.

The SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) Lambda variant rapidly diffused across Peru following its identification in December 2020, and had now spread worldwide. In this study, we investigated infodemiologic trends in symptomatology associated with the Coronavirus Disease 2019 (COVID-19) following the spread of SARS-CoV-2 Lambda variant in Peru, enabling infodemiologic surveillance of SARS-CoV-2 in regions with high circulation of this new variant. Weekly Google Trends scores were obtained for key symptom keywords between March 1st, 2020 and July 4th, 2021, whilst case count data were obtained from Peruvian Ministry of Health. Multiple time series linear regression was used to assess trends in each score series, using the week of December 27th as cutoff for emergence of the Lambda variant. The significance of such trends was tested for each time period, before and after the cutoff date. A total 2,075,484 confirmed SARS-CoV-2 infections in Peru in relation to Google Trends data were analyzed. After Lambda variant emergence, searches for "diarrhea" demonstrated a change from a negative to positive correlation with weekly case counts and anticipated dynamic changes in case counts by 1-5 weeks. Searches for "shortness of breath" and "headache" remained consistently positively correlated to weekly case counts before and after Lambda emergence. No changes in searches for other common cold symptoms were observed, while no specific trends were observed for "taste loss" or "smell loss". Diarrhea, headache, and shortness of breath appear to be the most important symptoms for infodemiologic tracking the current outbreak in Peru and other regions with high circulation of SARS-CoV-2 Lambda variant.

BackgroundPneumococcal vaccination (PCV13) for children (as well as older adults) in Russia was introduced in 2014, with no prior PCV7 use. While pneumonia hospitalization rates, both in children and adults didnt decrease in the following years, respiratory mortality rates declined with time. Moreover, there is a strong association between antibiotic, including multidrug resistance and PCV13 vaccine serotypes for S. pneumoniae in children in Russia, and presence of S. pneumoniae among sepsis cases in Russia during the recent years has been very low. Annual variability in influenza circulation may affect some of the changes in respiratory mortality rates, obscuring the trends in respiratory mortality related to pneumococcal vaccination. MethodsWe applied the inference method from our recent study of influenza-associated mortality in Russia to relate monthly respiratory mortality rates between 09/2010 and 08/2019 to monthly indices of influenza circulation and baseline rates of mortality not associated with influenza, allowing for a potential trend in the baseline rates starting 2015. ResultsBaseline rates of respiratory mortality not associated with influenza decreased with time starting from the 2014/15 season (with each season running from September to August), with the 2018/19 baseline rates of respiratory mortality per 100,000 individuals being lower by 12.41 (95% CI (10.6,14.2)) compared to the 2010-2014 period. ConclusionsWhile improvement in care might have contributed to the reduction in the rates of respiratory mortality not associated with influenza in Russia, the above temporally consistent reduction is compatible with the gradual replacement of vaccine serotypes in the transmission and carriage of S. pneumoniae following the introduction of PCV13. Further work is needed to better understand the impact of PCV13 on the epidemiology of respiratory infections and related mortality in Russia.

BackgroundAdults living with human immunodeficiency virus (ALWHIV) taking antiretrovirals (ART) have higher pneumococcal nasopharyngeal carriage and disease than adults without HIV (HIV-). To assess factors influencing high pneumococcal carriage prevalence and generate evidence base for evaluating future pneumococcal conjugate vaccine (PCV) strategies in ALWHIV, we estimated pneumococcal carriage acquisition and clearance rates in a high transmission and disease-burdened setting, at least 10 years after introducing infant PCV13 in routine immunisation. MethodsWe collected longitudinal nasopharyngeal swabs from age-and sex-matched 18-45-year-old HIV-adults, ALWHIV with ART experience of more than 1 year (ART>1y) or less than 3 months (ART<3m) from communities around Blantyre, Malawi. Samples were taken at baseline, and then weekly during the 16 visits over the study period. We employed classical culture microbiology to detect pneumococcal carriage and determined pneumococcal serotypes using latex agglutination. We fitted trajectories of serotype colonisation to multi-state Markov models to capture the dynamics of pneumococcal carriage adjusting for age, sex, number of household children under 5 years-old (<5y), social economic status (SES) and seasonality. ResultsAt baseline, 65 adults were enrolled in each of the three HIV groups irrespective of pneumococcal carriage status, totalling 195 adults of whom 51.8% were females, 25.6% cohabited with >1 child <5y, and 41.6% lived in low SES. Median age was 33y (interquartile range [IQR]: 25-37y). Baseline pneumococcal carriage prevalence of all serotypes as 31.3% of which non-PCV13 serotypes (NVT) (26.2%) was higher than PCV13 serotypes (VT) (5.1%). In a multivariate longitudinal analysis, pneumococcal carriage acquisition was higher in females than males (NVT [Hazard Ratio [HR]: 1.53, 95%CI:1.17-2.01]; VT [1.96, 1.11-3.49]). It was also higher in low than high SES (NVT [1.38, 1.03-1.83]; VT [2.06, 1.13-3.77]), in adults living with 2+ than 1 child <5y (VT [1.78, 1.05-3.01]), and in ALWHIV on ART>1y than HIV-adults (NVT [1.43, 1.01-2.02]). Moreover, ALWHIV on ART>1y cleared pneumococci slower than HIV-adults ([0.65, 0.47-0.90]). Residual VT 19F and 3 were highly acquired although NVT remained dominant. ConclusionsThe disproportionately high point prevalence of pneumococcal carriage in ALWHIV on ART>1y is likely due to impaired nasopharyngeal clearance resulting in prolonged carriage. Our findings provide baseline estimates for comparison of pneumococcal carriage dynamics after new PCV strategies in ALWHIV are implemented. Author summaryWe assessed rates of pneumococcal serotype carriage acquisition and clearance by fitting multi-state Markov models to pneumococcal colonisation trajectories comprising 3,152 nasopharyngeal samples from 195 adults aged 18-45 years in Blantyre, Malawi. Substantial acquisitions of VT and NVT in females and those living under low socioeconomic status were estimated, in addition to VT acquisition among adults living with at least two children in the house and NVT acquisition among ALWHIV on ART>1y. ALWHIV on ART>1y cleared overall carriage, and NVT in particular, slower than their HIV-counterparts. Residual VT serotypes 19F and 3 were highly acquired whereas 19A, 3, and 6A were carried for longer durations, still, NVT serotypes remained dominant, suggesting that PCV strategy in ALWHIV should consider expanded serotype coverage to tackle the remaining preventable burden of pneumococcal carriage and subsequent disease. The contribution of NVT carriage to the disproportionately high carriage prevalence in ALWHIV is substantial, though the underlying causal drivers for prolonged duration of carriage in ALWHIV on ART>1y warrant further investigation. We generate the evidence base for evaluating future pneumococcal vaccine strategies in ALWHIV.

IntroductionAs SARS-COV-2 and the disease COVID-19 is sweeping through countries after countries around the globe, it is critical to understand potential burden of a future outbreak in cities of Colombia. This pandemic has affected most of the countries in the world because the high global movement of individuals and excessive cost in interventions. ObjectiveUsing demographic data from city of Cali, disease epidemiological information from affected countries and mathematical models, we estimated the rate of initial exponential growth of new cases and the basic reproductive rate for a potential outbreak in city of Cali in Colombia. Materials and methodsWe used dynamical models with different modeling assumptions such as use of various types of interventions and/or epidemiological characteristics to compare and contrast the differences between Colombian cities and between Latin American countries. ResultsUnder the assumption of homogeneously mixing population and limited resources, we predicted expected number of infected, hospitalized, in Intensive Care Units (ICU) and deaths during this potential COVID-19 outbreak. Our results suggest that on a given day in Cali there may be up to around 73000 cases who might need hospitalization under no intervention. However, this number drastically reduces if we carry out only-isolation intervention (with 16 days of symptomatic infection; ~13,000 cases) versus both quarantining for 6 days and isolation within 16 days (~3500 cases). The peak in Cali will reach in 2-3 months. ConclusionsThe estimates from these studies provides different scenarios of outbreaks and can help Cali to be better prepared during the ongoing COVID-19 outbreak.

BackgroundIntensive screening and testing for COVID-19 could facilitate early detection and isolation of infected persons and thereby control the size of the epidemic. It could also facilitate earlier and more targeted therapy. These factors could plausibly reduce attributable mortality which was the hypothesis tested in this study. MethodsLinear regression was used to assess the country-level association between COVID-19 attributable mortality per 100 000 inhabitants (mortality/capita) and COVID-19 tests/capita (number of tests/100 000 inhabitants) controlling for the cumulative number of COVID-19 infections/100 000 inhabitants (cases/capita), the age of the epidemic (number of days between first case reported and 8 April), national health expenditure per capita and WHO world region. ResultsThe COVID-19 mortality rate varied between 0.3 and 3110 deaths/100 000 inhabitants (median 30, IQR 8-105). The intensity of testing per 100 000 also varied considerably (median 21,970, IQR 2,735-89,095) as did the number of COVID-19 cases per 100 000 (median 1,600, IQR 340-4,760 cases/100 000). In the multivariate model, the COVID-19 mortality rate was negatively associated with tests/capita (Coef. -0.036, 95% CI -0.047- -0.025) and positively associated with cases/capita (Coef. 0.093, 95% CI 0.819- 1.034). ConclusionsThe results are compatible with the hypothesis that intensive testing and isolation could play a role in reducing COVID-10 mortality rates.

IntroductionNon-pharmaceutical interventions (NPIs), which aimed to reduce transmission of SARS-CoV-2, also reduced the circulation of other respiratory pathogens. However, it remains unclear to what extent NPIs disrupted pneumococcal colonization in childcare settings. We investigated pneumococcal colonization dynamics in childcare centers in the Greater New Haven Area (USA) with varying levels of COVID-19-related NPI recommendations. MethodsWeekly, parent-collected saliva samples were obtained from children attending 8 childcare centers during Spring 2021 (February 2021-June 2021) and Winter/Spring 2021/22 (November 2021-June 2022). Samples were culture-enriched and tested using quantitative polymerase chain (qPCR) for pneumococcus targeting piaB, lytA, and pneumococcal serotypes. Trajectories of pneumococcal colonization were modeled using Markov models adjusted for age, sex, household size, ethnicity and study period. Bayes rule was used to adjust for false positivity of detecting non-pneumococcal signals in pneumococcal serotype-specific qPCR assays. ResultsA total of 1,100 saliva samples were collected from 100 children aged 0.3-5.9 years (median = 3.3 years, IQR = 1.8-4.6 years). Carriage dynamics based on detection of piaB and lytA were largely similar. Aggregated piaB-based carriage prevalence was higher during Winter/Spring 2021/22 (52.8%, 95% Confidence Interval: 49.4-56.3) than Spring 2021 (30.7%, 25.4-36.5). This increase in prevalence during Winter/Spring 2021/22 was driven by a higher proportion of high-density carriers, coinciding with less stringent NPI measures. Overall carriage acquisition rates were also higher during Winter/Spring 2021/22 than Spring 2021 (Hazard Ratio [HR]: 2.88, 1.09-7.60). The most commonly prevalent serotypes were 15B/C, 11A/D/E and 33F/A/37. ConclusionsWe observed distinct patterns of pneumococcal carriage between Spring 2021 and Winter/Spring 2021/22 of the COVID-19 pandemic, among children attending New Haven childcare centers. The increase in carriage prevalence coincided with the relaxation of COVID-19 NPI measures during Winter/Spring 2021/22 and an increase in local cases of certain respiratory viruses.