European Journal of Cardiovascular Medicine

The earliest description of an influenza-like illness can be traced back to Hippocrates, who reported a highly contagious febrile disease in northern Greece around 410 B.C.[1] Although such illnesses had been described for centuries, the term “influenza” was first used much later. During the 1357 epidemic in Florence, Italy, the disease was termed “influenza di freddo” or “cold influence,” reflecting contemporary beliefs about its cause. In 1414, French chroniclers documented an epidemic affecting nearly 100,000 people in Paris, attributing it to a “smelly and cold wind” (vent puant et tout plein de froidure) [1].

The most devastating influenza pandemic in history occurred in 1918, caused by an H1N1 virus of avian origin. It is estimated that nearly 500 million people—about one-third of the global population—were infected, and at least 50 million deaths were reported worldwide.[2] Since then, influenza viruses have remained an important cause of morbidity and mortality across the globe.

In March 2009, an outbreak of a novel H1N1 influenza A virus was reported in Mexico, soon spreading rapidly across continents.[3] This strain represented a quadruple reassortment of two swine, one avian, and one human influenza virus, resulting in a pathogen with pandemic potential. On 11 June 2009, the World Health Organization (WHO) declared H1N1 a global pandemic, acknowledging the simultaneous community-level outbreaks across more than 70 countries.[4]

India confirmed its first case of H1N1 influenza on 16 May 2009, in a man returning from New York via Dubai and Delhi, who tested positive in Hyderabad.[5] Within months, the infection disseminated widely across the country. Mortality data illustrate the fluctuating impact of the disease: 981 deaths in 2009, 1,763 in 2010, 75 in 2011, 405 in 2012, 699 in 2013, and 218 deaths in 2014 with 837 laboratory-confirmed cases.[6] These figures highlight the recurrent burden of H1N1 despite variations in intensity across different years.

Clinically, most individuals with H1N1 infection develop a self-limiting, influenza-like illness that resolves within a week.[7] However, a significant minority progress to severe disease, manifesting as progressive viral pneumonia, acute respiratory distress syndrome (ARDS), or multi-organ dysfunction, particularly in those with comorbid asthma or chronic obstructive pulmonary disease. According to WHO, deterioration in severe cases may occur within 3–5 days of symptom onset, and respiratory failure can ensue rapidly, often within 24 hours, necessitating intensive care admission.[8,9] Patients frequently require mechanical ventilation, and some may fail conventional ventilation, requiring advanced modalities such as high-frequency oscillatory ventilation or extracorporeal membrane oxygenation (ECMO).

Diagnosis of H1N1 is confirmed through reverse transcription polymerase chain reaction (RT-PCR), viral culture, or serological demonstration of rising neutralizing antibody titers.[10] Management involves a combination of strict isolation, adherence to infection control measures, supportive therapy, and prompt initiation of antiviral agents.[11]

Several Indian studies have assessed the clinical and epidemiological characteristics of H1N1, revealing variations in demographic distribution, clinical presentation, comorbidity burden, and outcomes across different regions and time periods. Given these differences, there remains a need to continually assess the disease profile in diverse populations. The present study was conducted with the objective of evaluating the clinical profile, comorbidities, radiological findings, and outcomes of RT-PCR–confirmed H1N1 patients in a tertiary care hospital setting.

This prospective Cross-sectional Analytical study was conducted in the Department of Internal Medicine at Max Super Specialty Hospital, Saket, New Delhi, over a period of 12 months from May 2019 to April 2020. The study population comprised patients of either gender admitted to the hospital during the study period who fulfilled the eligibility criteria. Patients aged 18 years and above presenting with signs and symptoms suggestive of swine flu and confirmed positive for H1N1 infection by reverse transcription polymerase chain reaction (RT-PCR) were included after obtaining informed consent. Patients younger than 18 years of age and those who did not consent to participate were excluded from the study.

The sample size was calculated based on a previous prospective observational study by Mehta et al. [12] conducted in Kochi, Kerala, where 16% of H1N1 positive patients required mechanical ventilation. Using this prevalence, with a 5% margin of error and 95% confidence interval, the minimum sample size was estimated to be 207. Accordingly, 207 patients meeting the inclusion and exclusion criteria were recruited.

Data were collected prospectively using a structured data collection form. Demographic details (age and sex), presenting symptoms, comorbid conditions, clinical examination findings, initial laboratory investigations, radiological features, treatment received, need for intensive care unit (ICU) admission, requirement of ventilatory support (invasive and non-invasive), and final outcomes were recorded.

The diagnosis of H1N1 infection was established using Real Time PCR. Samples included throat/nasal swabs collected in viral transport medium (VTM), bronchoalveolar lavage (BAL) fluid, endotracheal (ET) or tracheal secretions, and sputum. RNA extraction was performed using an automated Qiasymphony (Qiagen) platform with a 500 µl cell-free protocol, following pre-lysis procedures under biosafety level 3 precautions. The extraction process involved AVL buffer (560 µl), cRNA (5.6 µl), and specimen (140 µl), followed by vortexing, incubation at room temperature for 10 minutes, and automated RNA isolation. Each extraction run processed 24 samples within approximately 90 minutes. Detection was carried out using multiplex real-time RT-PCR on the Rotor-Gene Q system with the artus Infl./H1 LC/RG-RT PCR kit. This kit provides two ready-to-use systems for the detection of influenza A and B viral RNA and the novel influenza A (H1N1) 2009 strain.

The primary outcomes of interest were to identify the clinical profile and most common presenting symptoms of H1N1 infection, recognize laboratory manifestations, and describe radiological features on chest X-ray. The study protocol was reviewed and approved by the Institutional Ethics Committee, and the research was conducted in accordance with the Indian Council of Medical Research (ICMR) Ethical Guidelines for Biomedical Research on Human Participants (2017). Written informed consent was obtained from all participants.

Data were entered into Microsoft Excel and analyzed using the Statistical Package for Social Sciences (SPSS) version 21.0. Continuous variables were expressed as mean±standard deviation (SD), while categorical variables were presented as frequencies and percentages. Categorical variables were analyzed with the Chi-square test. A p-value of <0.05 was considered statistically significant

[Table 1] summarizes the demographic, clinical, comorbidity, radiological, laboratory, and outcome profile of the study population. Among 207 patients, males (64%) were more commonly affected than females (36%). The majority of cases occurred in the 51–60 years (32%) and 61–70 years (24%) age groups. Fever (88%) and dry cough (80%) were the predominant presenting symptoms, followed by breathlessness (43%). Hypertension (37%) and diabetes mellitus (33%) were the leading comorbidities, while COPD was present in 27% of cases. Chest X-ray most frequently showed ARDS (45%), with 39% having normal findings. Laboratory investigations revealed leukocytosis in 66% and anemia in 33% of patients. Nearly one-third of patients (28%) required ventilatory support during the course of illness. Majority were managed with non-invasive mechanical ventilation (NIMV) in 37(65%) patients, while 20(35%) patients required invasive mechanical ventilation.

Table 1- Demographic, Clinical, Comorbidity, Radiological, Laboratory, and Outcome Profile of RT-PCR Confirmed H1N1 Patients (n = 207)

[Table 2] Fever was the most common symptom among both survivors (87%) and non-survivors (100%), though the association was not statistically significant (p = 0.386). Dry cough was more frequent in survivors (81%) compared to non-survivors (58%), nearing statistical significance (p = 0.058). In contrast, breathlessness (100% vs. 39%), myalgia (92% vs. 27%), sore throat (83% vs. 16%), coryza (75% vs. 10%), and diarrhea (75% vs. 7%) were significantly more prevalent among non-survivors (all p < 0.001). Productive cough did not show a significant association with outcome (p = 0.240). These findings highlight that while fever was universal, symptoms such as breathlessness, myalgia, sore throat, coryza, and diarrhea were strongly associated with higher mortality.

Table 2- Association of presenting symptoms with final outcome in RT-PCR–confirmed H1N1 patients

[Table 3]shoed that Diabetes mellitus was present in 83% of non-survivors compared to 30% of survivors, while hypertension was noted in 75% of deaths versus 34% of survivors. Chronic obstructive pulmonary disease (COPD) was significantly more frequent among non-survivors (75%) than survivors (24%). Similarly, chronic kidney disease (67% vs. 8%), coronary artery disease (75% vs. 6%), chronic liver disease (75% vs. 2%), and hypothyroidism (58% vs. 2%) were strongly associated with mortality. Obesity was seen in 83% of non-survivors compared to only 5% of survivors. Immunosuppression was documented exclusively among non-survivors (42%), while none of the survivors had this condition. All these associations were statistically significant (p < 0.001), indicating that comorbidities played a crucial role in predicting adverse outcomes among H1N1 patients.

Table 3: Relationship of comorbidities with final outcome of study population.

[Table 4] demonstrated that Anemia was present in 92% of non-survivors compared to 29% of survivors. Leukocytosis was observed in all non-survivors (100%) versus 64% of survivors. Thrombocytopenia was significantly more frequent among non-survivors (75%) than survivors (8%). Similarly, abnormal liver function tests (67% vs. 4%) and abnormal kidney function tests (75% vs. 9%) were predominantly seen in patients who died. All these associations were statistically significant (p < 0.001), indicating that deranged hematological and biochemical parameters were strong predictors of mortality in H1N1 infection.

Table 4: Relationship of laboratory test result with final outcome of patients.

[Table 5] Among the 126 patients with abnormal radiographs, all non-survivors (100%) belonged to this group, whereas 114 patients (58%) survived. In contrast, none of the patients with normal chest X-rays (n = 81) died; all survived (42% of survivors). The association was statistically significant (p = 0.011).

Table 5- Relationship of abnormal chest X-ray findings with final outcome in RT-PCR–confirmed H1N1 patients

Since the control of the 2009 H1N1 pandemic, the global burden of cases has decreased, but India continues to report recurrent outbreaks with significant numbers of cases and deaths. The resurgence of H1N1 since 2015 has been concerning, with fluctuating case numbers but improved survival compared to the pandemic period. In 2016, 1,786 swab-positive cases with 265 deaths were reported, whereas in 2017, up to July, 12,460 cases with 600 deaths were recorded. Although the number of cases was higher, the case fatality rate reduced from 14.8% in 2016 to 4% in 2017.[13,14] The worst outbreak in India was seen in 2009–2010, when nearly 50,000 cases and 2,700 deaths occurred. This highlights that periodic re-emergence of H1N1 remains a significant public health issue. The present study was undertaken to evaluate the clinical profile, comorbid conditions, radiological findings, and outcomes of RT-PCR–confirmed H1N1 patients in a tertiary care hospital.

In our study, the most affected age group was 51–60 years (32%). A similar observation was made by Prasad S, et al. [15], who also reported maximum cases in this age group (25%). Male patients accounted for 64% of cases, while females constituted 36%. This distribution was similar to Rao R, et al. [16], who found 63.9% males and 36.1% females. Although more males were affected overall, fatality was higher among females (67% vs. 33%). This finding is consistent with Kumar TC, et al. [17], who also reported greater fatality among females, though Amaravathi KS, et al. [18] found higher mortality in males.

Fever (88%) and dry cough (80%) were the most common symptoms, followed by breathlessness (43%) and myalgia (31%). Symptom comparison with other Indian studies shows a similar trend, with fever being nearly universal.[18,15,16] Breathlessness, myalgia, sore throat, coryza, and diarrhea were significantly associated with mortality in our study. Kumar TC, et al. [17] also found breathlessness to be a predictor of adverse outcome.

Comorbidities were highly prevalent, with hypertension (37%), diabetes mellitus (33%), and COPD (27%) being the most common. All major comorbidities including CKD, CAD, CLD, hypothyroidism, obesity, and immunosuppression showed significant association with mortality. This is in line with previous Indian studies, though prevalence rates varied.[18,15,16] For example, Amaravathi KS, et al. [18] reported lower rates of hypertension (17%) and COPD (6%), whereas our study found higher prevalence.

Chest X-ray abnormalities were observed in 61% of patients, with ARDS being the most frequent finding (45%). All non-survivors had abnormal chest X-rays, and this association was statistically significant. Similar observations have been reported by Amaravathi KS, et al. [18] and Prasad S, et al. [15], confirming that radiological changes are important indicators of disease severity and poor outcome.

Ventilator support was required in 28% of patients. Non-invasive ventilation (NIMV) was sufficient for most (65%), while 35% required invasive ventilation. In comparison, Prasad S, et al. [15] reported invasive ventilation in 11.8% and non-invasive support in 21%, while Mehta AA, et al. [19] observed 16% of cases requiring mechanical ventilation.

The overall survival in our study was 94%, with 6% mortality. This is comparable to other Indian studies, such as Mehta AA, et al. [19] (93% survival), Prasad S, et al. [15] (91% survival), and Sharma A, et al. [20] (95.2% survival). However, some earlier studies, such as Maheshwari M, et al. [21], reported higher mortality rates (56%). This variation may be explained by differences in patient characteristics, healthcare facilities, and timing of antiviral initiation.

Overall, our findings suggest that H1N1 infection affects middle-aged adults more commonly, with comorbidities, abnormal laboratory parameters, radiological changes, and need for ventilatory support being strongly associated with poor outcomes. These results are consistent with other Indian studies and emphasize the importance of early identification and aggressive management of high-risk patients.

In this study, H1N1 infection was most common among patients in the fifth decade of life. Although male patients were more frequently affected, gender did not influence the final outcome. Fever (88%) and dry cough (80%) were the most frequent symptoms, but breathlessness, myalgia, sore throat, coryza, and diarrhea showed a significant association with mortality. Among comorbidities, diabetes mellitus, hypertension, COPD, chronic kidney disease, coronary artery disease, chronic liver disease, hypothyroidism, obesity, and immunosuppression were all significantly related to adverse outcomes. Laboratory abnormalities such as anemia, leukocytosis, thrombocytopenia, and deranged liver and kidney function tests were also more common in non-survivors. Chest X-ray findings were abnormal in 61% of cases, and abnormal radiographs were significantly associated with death. The overall mortality in the study was 6%. These results suggest that patients with comorbidities, abnormal laboratory parameters, and radiological changes require close monitoring, as their clinical course may be severe and unpredictable.

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