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ORIGINAL ARTICLE
Year : 2023 | Volume
: 9
| Issue : 2 | Page : 39-46
Post-COVID symptoms and recovery times in hospitalized mild and moderate COVID-19 patients
Rajashree Khot, Aastha Patil, Bharatsing Rathod, Sunita D Kumbhalkar, Prashant P Joshi
Department of Medicine, All India Institute of Medical Sciences, Nagpur, Maharashtra, India
Correspondence Address:
Dr. Rajashree Khot
Plot No. 52 Jayneeta, New Ramdaspeth, Nagpur - 440 010, Maharashtra
India
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/ijam.ijam_95_22
Settings and Design: Retrospective online cross-sectional analytical study.
Introduction: Infection with SARS-CoV-2 virus led to COVID-19 pandemic with varied clinical manifestations and multisystem involvement, which persisted beyond acute stage. To evaluate the post discharge symptoms in hospitalized mild and moderate COVID-19 patients during the initial phase of pandemic. Factors associated with post-COVID symptoms and delayed recovery times were determined.
Materials and Methods: One hundred and thirty-two hospitalized patients of mild or moderate COVID-19 infection diagnosed by a positive real-time polymerase chain reaction, responded to an online questionnaire. They were followed up monthly, telephonically for post-COVID symptoms and recovery times. Microsoft Excel-Student's t-test, Fischer's exact test, Chi-square test.
Results: The mean age of the patients was 51.14 ± 13.78 years with male: female ratio, 1: 0.29. 80.35% had post-acute COVID symptoms. Most frequent symptoms were cough in 37.9%, breathlessness in 36.4% and fatigue in 34.8%. New onset symptoms were insomnia in 16.67%, anxiety in10.6%, depression in 9.8%, loss of libido in 5.3%. Long COVID syndrome occurred in four patients. The factors significantly associated with post-COVID symptoms were older age, comorbidities, longer hospitalization, and moderate COVID infection, whereas delayed recovery times were associated with older age, female gender, and moderate COVID illness.
Conclusions: Post-COVID symptoms occur in majority of the patients. Persistent symptoms are dry cough, dyspnea, fatigue, anosmia, and ageusia. They are significantly associated with older age, underlying comorbidities, prolonged hospitalization, and moderate COVID infection. Complete recovery occurs in most patients but delayed recovery is seen in females, elderly, and moderate COVID infection. Few may develop long COVID syndrome.
The following core competencies are addressed in this article: Patient care and procedural skills, Medical knowledge.
Keywords: Delayed recovery times, moderate COVID infection, post-COVID symptoms, psychiatric, pulmonary
COVID-19 pandemic started in India with 3 cases detected in Kerala on January 23,2020. It spread like wildfire and resulted in affection of masses. Currently, there are 47379 (0.11%) active cases, 43967340 (98.71%) discharged cases and 528370 (1.19%) deaths in India as of date (September 20, 2022).[1] Although the mortality rates in India were low, the morbidity rates and patterns have not been assessed. The aftermath of COVID-19 continues.
As the outbreak occurred and Lockdown period was relaxed from June 15, 2020, the number of cases surged. The cases increased exponentially and the first wave of COVID set in. Majority of COVID-19 positive patients came with the symptoms of fever, dry cough and shortness of breath.[2] Some were asymptomatic as well. It was observed that in many patients the symptoms persisted for a long time. The short term effects and symptoms of COVID-19 are well known,[3] but the long term effects or the after effects of the viral infection are not yet clear. Increasing evidence suggests that infection with COVID-19 causes multisystem involvement. A study from Italy found that in patients who had recovered from COVID-19, 87.4% reported persistence of at least 1 symptom, particularly fatigue and dyspnea.[4] After the first wave receded, there were many patients who presented with persistence of symptoms post discharge and some reported new onset of symptoms; mostly psychological. As the lockdown restrictions continued partially, the outpatient attendance of the patients was less.
We wanted to study the symptoms experienced by our patients post discharge and whether the concept “complete recovery” is applicable to COVID-19 or the virus leaves some long term residual effects which are permanent and/or progressive. Most of the studies evaluated these symptoms in patients who had severe COVID infection or those who were admitted to Intensive care unit and survived. We observed that patients with mild COVID infection also had persistent post-COVID symptoms. We wanted to evaluate the clinical parameters associated with post-COVID symptoms and delayed recovery times in patients having mild or moderate COVID infection. Hence, this study was carried out by reaching out to our patients via Google forms and the frequency of post-COVID symptoms, recovery times and their clinical correlates were determined.
Materials and MethodsThis retrospective cross sectional analytical study was carried out from August 1, 2020, to April 30, 2021 (8 months), during the first COVID-19 pandemic wave, after approval from institutional ethical committee.
Study population
200 patients of COVID-19 diagnosed by a positive real-time polymerase chain reaction (RT-PCR), who were discharged from our hospital with mild or moderate COVID-19 infection as classified according to Ministry of Health and Family Welfare guidelines were sent a questionnaire developed as Google Forms, electronically, to know the post discharge symptoms and time taken for recovery from COVID-19 infection. Of these, 132 patients returned the forms, completely filled. The data from these patients was included in final analysis.
Eligibility criteria
Cases: 200 randomly selected COVID-19 positive by RT-PCR, Mild or Moderate patients ≥18 years of age who were admitted and discharged from COVID ward of our hospital during the period April 1, 2020–November 30, 2020.
Patients were excluded if they were less than 18 years of age, did not give consent, had severe COVID infection as per clinical criteria and/or a computed tomography (CT) severity score >15, did not return the Google forms or returned incompletely filled forms. Patients who had severe COVID infection were excluded from the study as they were expected to have prolonged respiratory symptoms, or post intensive care syndrome.
Methodology
200 randomly selected COVID-19 positive patients (mild and moderate) satisfying the inclusion and exclusion criteria were sent Google forms by electronic mail and a link for it on their WhatsApp number from 15 days post discharge till 180 days (6 months) post discharge at monthly intervals. The informed consent was included in the Google form and they were asked to fill the form online. The forms which were returned were included in the study if they were completely filled. The form also had a column for patients to share their experiences of COVID-19 as the disease and experience was new to all. Patients were followed up telephonically for 6 months post-covid to assess about recovery times. As Covid vaccine was not available during first wave, all the patients were unvaccinated.
Definitions
Mild COVID
Patients with uncomplicated upper respiratory tract infection, may have mild symptoms such as fever, cough, sore throat, nasal congestion, malaise, headache without evidence of breathlessness or hypoxia (normal saturation).[5]
Moderate COVID
Pneumonia with no signs of severe disease, adolescent or adult with presence of clinical features of dyspnea and/or hypoxia, fever, cough, including SpO2.[5]
As per treating physician's decision, X-ray chest was done in 82.8% of patients and around 55.3% of patients underwent high resolution CT (HRCT) of thorax. A CT severity score of 0–8 was considered as Mild COVID, 8–15 as Moderate COVID and 15-25 as severe COVID.[6] CT severity score was taken as a supportive tool for classification of illness into mild and moderate infection. Those with a CT severity score of more than 15 were excluded from the study.
Post-COVID symptoms
They were defined as symptoms which were present at the time of hospitalization and persisted after discharge and any new symptoms which developed within 1 month of discharge with no other cause for the same. Association of Factors associated with post-covid symptoms e.g., age, gender, severity of infection, comorbidities, etc., was determined.
Long COVID syndrome
If the COVID related symptoms during hospitalization or any new symptoms which developed within 1 month of discharge, persisted beyond a period of 6 months (180 days) were considered as long COVID syndrome.
Recovery times
They were defined as time required for the patient to be completely symptom free – mentally and physically and resume normal activities from the date of RT-PCR positivity for COVID-19. Association of factors with delayed recovery times e.g., Age, gender, severity of infection, comorbidities etc., was determined.
Development of online tool
The online tool was developed in the form of Google form which was peer reviewed and validated initially in a set of 25 patients chosen randomly from the discharge data of COVID wards. It included the basic demographic data, dates of testing, COVID-19 positivity, duration of hospitalization, key symptoms pre and post-COVID, comorbidities, Chest X-rays and HRCT or thoracic scan reports. Biochemistry reports like C reactive protein, serum ferritin reports were also asked for but more than 50% of the patients could not provide them. Hence, they could not be used for analysis. Provision was made for patients to describe their COVID experience in few lines.
Statistical analysis
Collected data was entered into MS-Excel. Descriptive statistics like proportions, mean, and standard deviation were used for continuous variables. For categorical variables, Chi-square test was used. The Mann–Whitney U test was used to compare differences between two groups when the dependent variable was not normally distributed. The confidence limit for significance was fixed at 95% level with P < 0.05.
ResultsBaseline characteristics
Out of 200 patients, 132 patients returned the forms duly filled. Majority of the patients were in the age group of 40–60 years and the mean age of the patients was 51.14 ± 13.78 years with male preponderance, M:F ratio being 1: 0.29. The mean age of females was 53.23 ± 9.6 years and males was 50.51 ± 7.2 years, with no statistically significant difference (P = 0.32). Mild COVID infection was observed in 76 (57.6%) patients and Moderate COVID infection in 56 (42.4%) patients. 50.7% of patients did not have any comorbidity whereas 49.3% of patients had either single or multiple comorbidities. Majority of the patients were hospitalized within 2 days of testing. The duration of hospitalization was more in patients with moderate COVID as compared to Mild COVID. The baseline characteristics of the patients have been shown in [Table 1].
Frequency of post-COVID symptoms and associated factors
Majority of the patients i.e., 106 (80.35%) had post-acute COVID symptoms (PACS) after discharge. Most common symptoms were cough in 37.9%, breathlessness in 36.4% and fatigue in 34.8% [Figure 1]. New onset symptoms were mostly psychiatric [Figure 2].
Anxiety occurred in 14/132 (10.6%) and depression in 13/132 (9.8%). Long COVID syndrome i.e., persistence of symptoms beyond 6 months was observed in only 4 patients. Dry cough was commonly observed in patients with moderate COVID. Breathlessness was associated with dry cough. Breathlessness persisted in patients of moderate COVID who received supplemental oxygen during hospitalization. 15.4% of moderate COVID patients required home oxygen therapy for 10–15 days after discharge from hospital. The factors which were significantly associated with development of post-COVID symptoms were older age, presence of comorbidities, increased duration of hospitalization, and Moderate COVID infection [Table 2].
Young patients usually had persistence of Anosmia and Ageusia for a duration of 21 to 42 days. Only 1 patient did not have recovery of anosmia. Mean CT score in patients without post-COVID symptoms was 1.69 ± 2.72 and in those with post-COVID symptoms was 6.78 ± 5.05, the difference was highly significant statistically (P < 0.0001).
Recovery times from acute COVID infection and their clinical correlates
The recovery period varied from 10 days to 6 months. Most of the patients; 40 (30.3%) recovered in a period of 1 to 2 months (30–60 days). Most of the patients with mild COVID, 34 (25.75%) recovered within a month i.e., 16–30 days. The mean duration of recovery was 34.73 ± 22.4 days in mild COVID illness. It was more because Anosmia persisted for 34.67 ± 9.5 days and ageusia for a mean of 21 ± 5.8 days. Mean recovery time in moderate COVID infection was 64.01 ± 32.5 days. Ninety percent of the patients recovered within 3 months. Recovery times were more in patients who had pulmonary symptoms. Those who had breathlessness required a mean time of 78 ± 36.4 days and for cough it was 66.53 ± 32.9 days. The significant clinical correlates of delayed recovery were older age, female gender, increased duration of hospitalization and moderate type of COVID infection [Table 3].
Individual patient experiences
Patients' experiences about COVID and post-covid symptoms
The patients also wrote a short narrative about their COVID experience. Those who had mild symptoms equated it to simple flu like experience with a slightly long duration of recovery. Patients reported fatigue as the most disabling symptom which resulted in delayed recovery and increased time of return to work. Persistence of fatigue, generalized weakness and body-ache were the major symptoms which resulted in development of anxiety and depression among patients. Patients had difficulty in getting a bed in the hospital. Few patients expressed relief that they survived the illness. Only 1 patient commented that his positive attitude helped him recover from illness. Many patients reported that the post-covid symptoms experienced by them, especially fatigue and mental stress, were something they had never experienced before. They were also dissatisfied with the lack of medications and effective treatment for the same.
DiscussionFrom March 2022, the COVID 19 Pandemic spread its tentacles in the Indian subcontinent. India with its large population and limited resources, was at risk of devastating effects of the acute illness and its aftermath. Initially, the infection could be contained due to strict lockdown measures. The country experienced the first wave of COVID 19 pandemic when the lockdown measures were relaxed. The world was still learning about the infection and definitive protocols were yet to be developed. The local health authorities recommended hospitalization and admission of patients with Mild infection also. The first reports of PACS were from China and slowly poured in from all over the globe. We planned this study with the aim of studying the post-covid symptoms in hospitalized patients with Mild and Moderate COVID infection. Patients with severe COVID were excluded as they had a severe respiratory illness, received mechanical ventilatory support, had prolonged hospitalization and were expected to have delayed recovery.
The definitions of post-covid syndrome were unclear, so we defined it including the primary COVID symptoms which persisted after discharge from the hospital and some new symptoms for which no other cause could be found. Our study was limited to 6 months or 180 days post-covid, with the day of RT-PCR positivity as Day 1. United Kingdom's National Institute for Health and Care Excellence's guideline on long COVID provides two definitions of post-acute COVID-19: (1) ongoing symptomatic COVID-19 for people who still have symptoms between 4 and 12 weeks after the start of acute symptoms; and (2) post-COVID-19 syndrome for people who still have symptoms for more than 12 weeks after the start of acute symptoms.[7] Initially PACS persisting beyond 12 weeks was labelled as chronic COVID syndrome. But this has been further subclassified and now symptoms persisting beyond 180 days are called as long COVID syndrome.[8] In our study only 4 patients had symptoms beyond 6 months. All of them had moderate COVID infection with predominantly respiratory symptoms of chronic cough and dyspnea.
COVID-19 resulted in affection of multiple systems and clinical presentations were varied. Similar to the post-acute viral syndromes described in survivors of other virulent coronavirus epidemics like MERS and SARS CoV1, it was anticipated that there would be persistent symptoms after acute COVID-19. Potential mechanisms contributing to the pathophysiology of post-acute COVID-19 include: (1) virus-specific pathophysiologic changes; (2) immunologic aberrations and inflammatory damage in response to the acute infection; and (3) expected sequelae of post-critical illness.[9]
In the post-acute COVID-19 US study, based on telephonic survey of survivors of COVID-19, out of 488 patients 32.6% of patients reported persistent symptoms, including 18.9% with new or worsened symptoms. Dyspnea while walking up the stairs (22.9%) was most reported, while other symptoms included cough (15.4%) and persistent loss of taste and/or smell (13.1%).[10] In our study, out of 132 patients 106 (80.35%) reported post-covid symptoms. The new onset symptoms were lack of concentration, loss of libido, insomnia and mostly psychiatric like anxiety and depression. Anosmia and Ageusia were commonly observed in COVID 19 infection. In our patients also, anosmia and ageusia occurred with increased frequency and they persisted also for a longer duration. Some studies have reported an early recovery and some studies have reported persistence of anosmia and ageusia in 33.8% and 26.4%, respectively.[11] It was found to be more common in females and our observation was same. It has been hypothesized that a decrease in the sensitivity of the sensory neurons as well as the coexpression of angiotensin-converting enzyme 2 and transmembrane serine protease 2 in the alveolar epithelial cells are the main causes of olfactory-gustatory disorders.
Dry cough and dyspnea have been persistent in patients who had more severe illness with predominantly pulmonary manifestations of COVID. 37.9% of our patients had cough and 36.4% had dyspnea of variable degree after discharge. Of these, 74.6% had moderate COVID illness. Prevalence of persistent dyspnea varies from 5% to 81% after hospitalization. Around ~ 14% non-hospitalized patients with mild COVID-19 also have dyspnea. The mechanisms of dyspnea after COVID-19 are multifactorial, including parenchymal sequelae, dysfunctional breathing, cardiovascular dysfunction and muscular deconditioning. Cough although less common than dyspnea is known to persist for weeks or months after SARS-CoV-2 infection and has been reported in 2%–42% of patients.[12] In a large study conducted on patients 11 months after discharge, no clinical or hospitalization factors were associated with long-term post-COVID-19 cough.[13] In a recent review, Song et al. hypothesized that cough after COVID-19 was due to activation of the vagal sensory nerves, which leads to a cough hypersensitivity state and to neuroinflammatory events in the brain.[14]
Constitutional symptoms were very disabling for the patients and resulted in poor quality of life. Fatigue was the most frequent post-covid symptom and persisted for a mean duration of 72 ± 8 days (60-90 days). In very early stages, Carfi et al. reported fatigue in 53.1% of patients and 44.1% had worsened quality of life.[4] Similar to our findings of post discharge symptoms in 80.35%, an early study from Wuhan, China also reported at least one symptom at 6 months in 76% of their patients. Fatigue or muscle weakness (63%) and sleep difficulties (26%) were the most common symptoms. Anxiety or depression was reported among 23% of patients. They also evaluated patients who had severe illness and found respiratory symptoms and diffusion abnormalities in them.[15] A report published by the Centers for Disease Control and Prevention described persistent symptoms in patients with predominantly mild COVID-19. The common symptoms were cough (43%), fatigue (35%), and dyspnea (29%). A total of 95 (35%) patients reported not having returned to their baseline state of health. They also found a statistically significant association between underlying chronic medical conditions, obesity and underlying psychiatric condition and delayed recovery leading to delayed return to work.[16] In our study the statistically significant factors associated with development of post-covid symptoms were Older age, increased duration of hospitalization, presence of comorbidities and moderate COVID-19 infection.
A more serious complication observed in children who had mild COVID infection was multi-system inflammatory syndrome (MIS). There have been scarce reports of MIS in adults, especially young adults.[17] It occurs several months after COVID-19 infection and is a manifestation of post-covid syndrome. We did not find MIS in adults after first COVID wave, which was due to Beta variant of the virus.
Complete recovery from COVID occurred in 128 (96.9%) out of 132 patients. The mean recovery time was 46.17 ± 15.3 days. Recovery times were less in patients presenting with fever and constitutional symptoms and mild COVID infection. Recovery times were more in patients who had pulmonary symptoms; Breathlessness and cough. Long COVID was present in only 4 patients with moderate COVID illness. Many studies have shown that even for mild illness post-COVID symptoms persisted beyond 30 days, and they were more with increasing severity of illness. Cirulli et al. reported that 36.1% COVID patients had symptoms lasting for more than 30 days and 14.8% had at least one symptom after 90 days.[18] A population based cohort study from Zurich reported that female gender, severe symptoms during acute illness and presence of comorbidities were associated with nonrecovery from COVID at six to eight months after SARS-CoV-2 infection. They did not find an association of age or initial hospitalization with nonrecovery.[19] We observed a statistically significant delay in recovery times in older patients, females, those with moderate COVID illness and consequent longer duration of hospitalization.
Halpin et al. conducted the first comprehensive study in United Kingdom on post discharge symptoms and rehabilitation needs in COVID patients. They measured the quality of life in patients assessing mobility, self-care, usual activities, pain/discomfort, and psychological symptoms, and observed the clinically significant decrease in their cohort. It reflected the impact of the illness on quality of life and health burden to the economy.[20]
Study limitations
This study had several limitations. It was a retrospective online study. Patients reporting was the basis of this study. This study was carried out during the first wave of COVID when the treatment protocols were being changed frequently consequent to the new information about COVID coming from all over the globe. Association of biochemical and hematological parameters with post-COVID symptoms was not done due to lack of data. Physical follow-up with necessary investigations was not done as patients were reluctant to attend the hospital.
ConclusionsPost-covid symptoms were reported by majority of hospitalized patients with mild as well as moderate COVID-19 infection during the first wave of COVID-19 pandemic. Breathlessness, cough, fatigue, anosmia, ageusia were the common symptoms which persisted for long. New onset symptoms were mainly psychiatric; anxiety, depression, lack of concentration and loss of libido. However, most of the patients recovered completely by 3 months and Long COVID was rare. Recovery times were delayed in older patients, females, moderate COVID infection and greater duration of hospitalization.
There is a need for surveillance for post-covid symptoms which persist for months after the illness. They may impact the quality of life of patients resulting in considerable socio-economic and health burden. A multidisciplinary approach and protocol needs to be formulated for management of patients with post-acute COVID and Long COVID syndromes.
Acknowledgment
We are grateful to Major Gen (Dr) Vibha Dutta SM, Director and CEO, All India Institute of Medical Sciences, Nagpur for her encouragement and continuous support.
Financial support and sponsorship
Self and All India Institute of Medical Sciences, Nagpur.
Conflicts of interest
There are no conflicts of interest.
Ethical conduct of research
The research protocol was approved by the Institutional Ethics Committee. This study was done according to the reporting quality, formatting, and reproducibility guidelines set forth by the EQUATOR Network.
References
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