Clinical Spectrum, Geographical Variability of COVID-19, and its Implications

The coronavirus disease 2019 (COVID-19) pandemic has triggered a worldwide unprecedented public health crisis. Initially, COVID-19 was considered a disease of the respiratory system, as fever and at least one respiratory symptom was used to identify a suspected COVID-19 case. But there are now numerous reports of COVID-19 patients presenting with myriads of extra-pulmonary symptoms, however, a substantial number of patients are asymptomatic. Additionally, there are significant clinical and epidemiological variations of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection across different geographical locations. The updated re-search, thus, challenges the existing surveillance system that is mainly based on fever and respiratory symptoms. As countries are coming out of lockdown to save economic fallout, a revised surveillance strategy is required to effectively identify and isolate the infected patients. Besides, since developing countries are becoming the new epicenters of pandemic and there are limited resources for RT-PCR based tests, documenting the clinical spectrum can play a vital role in the syndromic clinical diagnosis of COVID-19. A plethora of atypical symptoms also aids in guiding better treatment and remains as a source for further research. It is, therefore, crucial to understand the com-mon and uncommon clinical manifestations of SARS-COV-2 infection and its variability across different geographic regions.Copyright © 2021 Bentham Science Publishers.

Comparative study of clinical features and vaccination status in Omicron and non-Omicron infected patients during the third wave in Mumbai, India.

Objectives: The Omicron variant-mediated COVID-19 wave is responsible for a global tsunami of cases. There is scarce data about the clinical and epidemiological characteristic analyses of the third wave. We present the data of COVID-19 patients from Mumbai region during the early third wave by taking S-gene target failure (SGTF) as a proxy for probable Omicron cases. Methods: We collected retrospective data of RT-PCR-confirmed (COVID-19) patients, and measured the proportion of possible Omicron cases by SGTF. We segregated and analyzed the clinical and lab data of patients with outcomes such as differing symptoms, vaccination coverage, previous infection, and travel history. We also performed a trend analysis of Mumbai's COVID-19 data before and during the third wave. Results: All patients had mild clinical symptoms while few were asymptomatic. Myalgia was more significantly present in SGTF/Omicron cases compared to non-SGTF/Delta patients. Out of the total 101 COVID-positive individuals, 94 individuals (93%) had taken two doses of COVID vaccine. Among these 94 individuals, 9 (8.9%) had been previously infected with COVID 19 in the first or second waves. 77.7% of the previously infected were now infected with Omicron variant and only 22.3% by a non-Omicron variant. Conclusion: Rapid rise and fall during the third wave in Mumbai was due to Omicron cases gradually replacing Delta. The overall milder clinical spectrum in both Omicron and Delta cases imply that vaccines might not be effective against re-infection but can attenuate disease severity and mortality, as evident by high coverage of vaccination in the country.

Kinetics of humoral immune response over 17 months of COVID-19 pandemic in a large cohort of healthcare workers in Spain: the ProHEpiC-19 study.

BACKGROUND: Understanding the immune response to the SARS-CoV-2 virus is critical for efficient monitoring and control strategies. The ProHEpic-19 cohort provides a fine-grained description of the kinetics of antibodies after SARS-CoV-2 infection with an exceptional resolution over 17 months. METHODS: We established a cohort of 769 healthcare workers including healthy and infected with SARS-CoV-2 in northern Barcelona to determine the kinetics of the IgM against the nucleocapsid (N) and the IgG against the N and spike (S) of SARS-CoV-2 in infected healthcare workers. The study period was from 5 May 2020 to 11 November 2021.We used non-linear mixed models to investigate the kinetics of IgG and IgM measured at nine time points over 17 months from the date of diagnosis. The model included factors of time, gender, and disease severity (asymptomatic, mild-moderate, severe-critical) to assess their effects and their interactions. FINDINGS: 474 of the 769 participants (61.6%) became infected with SARS-CoV-2. Significant effects of gender and disease severity were found for the levels of all three antibodies. Median IgM(N) levels were already below the positivity threshold in patients with asymptomatic and mild-moderate disease at day 270 after the diagnosis, while IgG(N and S) levels remained positive at least until days 450 and 270, respectively. Kinetic modelling showed a general rise in both IgM(N) and IgG(N) levels up to day 30, followed by a decay with a rate depending on disease severity. IgG(S) levels remained relatively constant from day 15 over time. INTERPRETATION: IgM(N) and IgG(N, S) SARS-CoV-2 antibodies showed a heterogeneous kinetics over the 17 months. Only the IgG(S) showed a stable increase, and the levels and the kinetics of antibodies varied according to disease severity. The kinetics of IgM and IgG observed over a year also varied by clinical spectrum can be very useful for public health policies around vaccination criteria in adult population. FUNDING: Regional Ministry of Health of the Generalitat de Catalunya (Call COVID19-PoC SLT16_04; NCT04885478).

Clinical spectrum and short-term outcomes of multisystem inflammatory syndrome in children in a south Indian hospital.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a new hyperinflammatory variant that evolved during the coronavirus disease 2019 pandemic. Although the precise pathophysiology of MIS-C is uncertain, it is thought to be due to immune dysregulation occurring after recovery from acute infection. PURPOSE: Our study aimed to analyze the clinical spectrum, laboratory parameters, imaging characteristics, treatment strategies, and short-term outcomes of children with a diagnosis of MIS-C. METHODS: This retrospective and prospective observational study included children less than 16 years of age who were admitted to the pediatric unit of a tertiary care teaching hospital in south India between August 2020 to January 2021 with a diagnosis of MIS-C according to World Health Organization criteria. RESULTS: Twenty-one children were included in the analysis; all had fever with variable combinations of other symptoms. The mean age was 6.9 years; 71.4% were male. Gastrointestinal (80.9%) and cardiovascular (80.9%) systems were the most commonly affected. The majority of children had elevated inflammatory markers, and 16 (76.2%) had echocardiographic abnormalities mimicking Kawasaki disease. Eleven children (52.4%) required intensive care admission, 3 (14.3%) required supplemental oxygen, and 4 (19%) required inotropes. Nine (42.9%) were treated with intravenous immunoglobulin alone, 6 (28.6%) with steroids alone, and 3 (14.3%) with steroids and immunoglobulin. The median hospital stay was 6 days; there were no fatalities. Overweight/obesity, elevated ferritin, and mucocutaneous involvement were significantly associated with a prolonged hospital stay (≥7 days). Sixteen children (76.2%) were followed up till now and all of them had no clinical concerns. CONCLUSION: MIS-C is an emerging disease with variable presentation. A high index of suspicion is necessary for its early identification and appropriate management. Further research is essential for developing optimal treatment strategies.

How is the iceberg of COVID-19? Results from a rapid literature review.

Background: Given the various reports of the clinical spectrum of the disease, the aim of the present study was to determine possible scenarios of Coronavirus 2019 (COVID-19) iceberg using published articles. Methods: The present study was a rapid review of all international databases, including PubMed (Medline), Scopus, Web of Sciences, Embase, and Cochrane Library from January 1 to October 30, 2020. Results: In this review, 7 scenarios were considered for COVID-19 iceberg, in which the range of fatality percentage was estimated to be 0.5% to 7%, the range of asymptomatic cases 1% to 88.6%, the range of cases with mild symptoms 8% to 78%, no symptoms 1 % to 90 %, the range of intensive care unit (ICU) admission was 0.5% to 14.2%, and finally the intubation percentage was estimated to be 0.2% to 12.2%. The Scenarios Diamond Princess Cruise Ship and Iceland are closer to the reality of the clinical spectrum of COVID-19 around the world, which represent 0.6% and 0.5% of deaths, 0.7% and 1% of intubations, 2.5% and 9.7% of ICU admissions, 1.1% and 6% of hospitalizations, 15% and 31% of cases with mild symptoms, and finally 56.9% and 75% of asymptomatic cases of COVID-19, respectively, which should now be considered as the basis of the clinical knowledge of the disease. Conclusion: Understanding the clinical spectrum and natural knowledge of the disease and paying attention to asymptomatic or mild-symptom cases can help to make better decisions and develop more effective interventions to control COVID-19.

Epidemiology, clinical spectrum, viral kinetics and impact of COVID-19 in the Asia-Pacific region.

COVID-19 has hit the world by surprise, causing substantial mortality and morbidity since 2020. This narrative review aims to provide an overview of the epidemiology, induced impact, viral kinetics and clinical spectrum of COVID-19 in the Asia-Pacific Region, focusing on regions previously exposed to outbreaks of coronavirus. COVID-19 progressed differently by regions, with some (such as China and Taiwan) featured by one to two epidemic waves and some (such as Hong Kong and South Korea) featured by multiple waves. There has been no consensus on the estimates of important epidemiological time intervals or proportions, such that using them for making inferences should be done with caution. Viral loads of patients with COVID-19 peak in the first week of illness around days 2 to 4 and hence there is very high transmission potential causing community outbreaks. Various strategies such as government-guided and suppress-and-lift strategies, trigger-based/suppression approaches and alert systems have been employed to guide the adoption and easing of control measures. Asymptomatic and pre-symptomatic transmission is a hallmark of COVID-19. Identification and isolation of symptomatic patients alone is not effective in controlling the ongoing outbreaks. However, early, prompt and coordinated enactment predisposed regions to successful disease containment. Mass COVID-19 vaccinations are likely to be the light at the end of the tunnel. There is a need to review what we have learnt in this pandemic and examine how to transfer and improve existing knowledge for ongoing and future epidemics.

Epidemiologic, clinical, and laboratory findings of the COVID-19 in the current pandemic: systematic review and meta-analysis.

BACKGROUND: The COVID-19 pandemic has affected the world deeply, with more than 14,000,000 people infected and nearly 600,000 deaths. This review aimed to summarize the epidemiologic traits, clinical spectrum, CT results and laboratory findings of the COVID-19 pandemic. METHODS: We scoped for relevant literatures published during 1st December 2019 to 16th July 2020 based on three databases using English and Chinese languages. We reviewed and analyzed the relevant outcomes. RESULTS: The COVID-19 pandemic was found to have a higher transmission rate compared to SARS and MERS and involved 4 stages of evolution. The basic reproduction number (R0) is 3.32 (95% CI:3.24-3.39), the incubation period was 5.24 days (95% CI:3.97-6.50, 5 studies) on average, and the average time for symptoms onset varied by countries. Common clinical spectrums identified included fever (38.1-39.0 °C), cough and fatigue, with Acute Respiratory Distress Syndrome (ARDS) being the most common complication reported. Body temperatures above 39.0 °C, dyspnea, and anorexia were more common symptoms in severe patients. Aged over 65 years old, having co-morbidities, and developing complications were the commonest high-risk factors associated with severe conditions. Leucopenia and lymphopenia were the most common signs of infection while liver and kidney damage were rare but may cause bad outcomes for patients. The bilateral, multifocal Ground-Glass Opacification (GGO) on peripheral, and the consolidative pulmonary opacity were the most frequent CT results and the tendency of mortality rates differed by region. CONCLUSIONS: We provided a bird's-eye view of the COVID-19 during the current pandemic, which will help better understanding the key traits of the disease. The findings could be used for disease's future research, control and prevention.

Epidemiologic, Clinical, and Laboratory Findings of the COVID-19 in the current pandemic.

BACKGROUND: The COVID-19 caused the pandemic affected the world deeply, with more than 3,000,000 people infected and nearly 200,000 deaths. This article aimed to summarize the epidemiologic traits, clinical spectrum, CT results and laboratory findings of COVID-19 pandemic. METHODS: We scoped for relevant literatures published during 1st Dec 2019 to 23rd Apr 2020 based on four databases by using English and Chinese. The evidence was synthesized narratively. RESULTS: The COVID-19 pandemic was found to have a higher transmission rate compared to SARS and MERS, and involved 4 stages of evolution. The basic reproduction number (R0) is 3.32 (95% CI:3.24-3.39) and the incubation period was 5.24 days (95% CI:3.97-6.50, 5 studies) on average, and the average time for symptoms onset varied by countries. Common clinical spectrums identified included fever (38.1-39.0°C), cough and fatigue, with Acute Respiratory Distress Syndrome (ARDS) being the most common complication reported. Body temperatures above 39.0 °C, dyspnea, and anorexia were more common symptoms in severe patients. Aged over 60 years old, having co-morbidities, and developing complications were the commonest high-risk factors associated with severe conditions. Leucopenia and lymphopenia were the most common signs of infection while liver and kidney damage were rare but may cause bad outcomes for patients. The bilateral, multifocal Ground-Glass Opacification (GGO) on peripheral, and the consolidative pulmonary opacity were the most frequent CT results and the tendency of mortality rates differed by region. CONCLUSIONS: We provided a bird's-eye view of the COVID-19 during the current pandemic, which will help better understanding the key traits of the disease. The findings could be used for disease's future research, control and prevention.