The world has encountered a cluster of atypical pneumonia cases, on December 31, 2019, due to a novel coronavirus, later named as severe acute respiratory syndrome 2 (SARS-CoV-2).
The coronavirus disease 2019 (COVID-19) pandemic resulted in a significant burden globally. Its effects include high rates of infection, death, financial burden, stress related to known and many unknown information sources, and fear of uncertainty regarding continued impact.
Most people who have COVID-19 recover completely within a few weeks. However, some people, even those who had mild disease, continue to experience symptoms after their recovery. They describe themselves as “long haulers” and the conditions have been called post-COVID-19 syndrome or “long COVID-19.” Patients with “long COVID” experience a wide range of physical and mental/psychological symptoms. The World Health Organization defines that the post COVID-19 condition occurs in individuals with a history of probable or confirmed SARS CoV 2 infection, within 3 months from the onset of COVID-19 with these symptoms lasting 2 months and that cannot be explained by an alternative diagnosis. Common symptoms not only include fatigue, shortness of breath, cognitive dysfunction but also others and generally have an impact on everyday functioning. Pooled prevalence data revealed that the most prevalent reported symptoms were fatigue, shortness of breath, muscle pain, joint pain, headache, cough, chest pain, altered smell, altered taste, and diarrhea. Other common symptoms were cognitive impairment, memory loss, anxiety, and sleep disorders. Beyond symptoms and complications, people with long COVID often experienced compromised quality of life, mental health, and livelihood issues. Those affected may require multidisciplinary care involving the long-term monitoring of symptoms, to identify potential complications, physical rehabilitation, mental health, and social services support.
In the middle of this unprecedented crisis of COVID-19, health-care workers (HCWs) faced many challenges treating patients with COVID-19, which included reducing the spread of infection, developing suitable strategies, and formulating plans. The psychological burden and overall wellness of HCWs have received heightened awareness in news and research publications with research continuing to show high rates of burnout, psychological stress, and even suicide. The ability of HCWs to adequately cope with stressors is important for their patients, families, and themselves. Providers vary in psychological resilience, which is the ability to positively adapt to adversity. Although research on the impact of COVID 19 and the consequences of acute infection in health-care workers (HCWs) has been done, not much is known of the long-term manifestations of COVID infection in HCWs.
In this context, we have set to report the manifestations of the long-COVID among health-care personnel residing in a tertiary medical teaching hospital campus, who were followed up for 1½ years. The aim of this study is to describe the long-term health consequences HCWs who have recovered from COVID-19 but were symptomatic and to evaluate the associated factors contributing to the same.
MATERIALS AND METHODS
This study was conducted at a medical college hospital which was designated by the state government as COVID hospital for admitting and treating suspected and confirmed patients of SARS-CoV-2 infection. The study population consisted of HCWs including doctors, nurses, paramedical staff, and administrative staff who are directly or indirectly involved in patient care. All respondents are cases who have been tested positive for COVID infection treated and discharged after recovery.
This was a longitudinal, prospective study of 1½ years study period followed up at weekly intervals until remission of the persisting symptoms in the COVID clinic for follow-up cases of COVID patients postdischarge by a senior physician (VRYJ). This would address the recall bias having followed the cases prospectively. All participants have given informed consent before being enrolled in the study. Ethical clearance was obtained from the institutional ethical committee.
Disease severity was classified as mild, moderate, severe, and critical, according to the World Health Organization (WHO) definition. A detailed postdischarge clinical history was collected, through a standardized questionnaire focused on the persistence of symptoms potentially related to recent SARS-CoV-2 infection. Symptom count included any self-reported symptoms persisting at the time of the follow-up visits. Postdischarge symptoms resolving before the first visit were excluded. Data collection included any hospital readmissions for any persisting symptoms, with post-COVID discharge manifestations being ascertained by medical record review, or alternatively, they were self-reported as per the questionnaire. A full physical examination of the individuals was performed by a senior physician. Appropriate investigations relevant to each case were done and noted, mainly dictated by clinical diagnosis. Complete blood count, coagulation profile, serum biochemical tests and serum inflammatory markers, and arterial blood gas tests were ordered in readmission cases and in those wherever deemed necessary and patients being agreeable for the tests. Whenever the respondents reported of stress, fear, and other psychiatric symptoms, they were referred to a psychiatrist, and after an interview, psychiatric diagnosis was made according to the International Classification of Diseases-10 criteria. Cognitive response and altered mental status assessment were done based on the clinical history and mental status examination, which includes higher cognitive functioning assessment done by both physician and psychiatrist.
Validated questionnaire was used to document the clinical manifestations. A health-related quality of life scale was used to assess the quality of life. It is a 14-item questionnaire consisting of scores on modules which includes Healthy days core module and Activity Limitations Module. It encompasses objective and subjective well-being dimensions. Objective well-being measures include quantity or frequency of items such as number of times the patients were admitted to the hospital, the distance a patient can walk, or the ability to climb the stairs. The subjective well-being includes assessments by patient himself or herself, such as level of pain or distress, level of satisfaction with their daily activities, and leisure time.
All 2000 health-care personnel had free access to avail medical services and treatment. With all the necessary safety precautions in place, 78 HCWs were tested positive with COVID-19 infection in both first and second waves of the COVID infection in our country. Among these, 41 affected individuals had given informed consent to be followed up for more than a year (1 year, 6 months) and were included in the study. Out of the 41 cases, 19 HCWS had long COVID according to the WHO definition of long COVID.
Clinical and laboratory data and the response to questionnaire were subjected to descriptive, statistical analysis. Data were entered in Microsoft Excel Sheet and further statistical analysis was done using STATA 14 (Stata Corp., College Station, Texas, USA). The descriptive data were analysed as follows: categorical data were analysed using percentages, and the continuous data were analysed using mean and standard deviation.
Out of the 41 health-care personnel, majority were male (73.17%) and were aged >50 years (51.22%). The mean of age distribution was 50.1 ± 11.8 years with an SD of 11.8 [Table 1]. Majority of the health care personnel were doctors (48.78%) [Table 2]. Most of the respondents reported nonspecific persisting symptoms. Majority reported fatigue, generalized weakness, shortness of breath, chest pain, vomiting, and fever [Table 3]. Fatigue was described as tiredness brought by exertion or independent of it. Generalized weakness was described as the loss of muscle strength. Other common symptoms included palpitations, disorders of smell and taste, sleep disturbances, reduced appetite, altered mental state, and persistent cold and cough. Few of the health-care personnel also had psychiatric problems such as depression and anxiety, with fear of being reinfected, with COVID-19 being predominant. The duration of long COVID symptoms had a mean of 5.243 months and SD of 0.982. Symptoms persisted for 4–7 months in the all-HCWs with post-acute COVID infection in our study. The mean and SD of follow-up period were 11.219 months and 3.346, respectively. At the time of the follow-up visits, 4 months following hospital discharge, (84%) had at least one persistent symptom, and 18/41 (43.9%) reported more than two symptoms. In our study, the persistence of symptoms was not related to COVID-19 severity or length of hospital stay.
With the health related quality of life, 73.1% of the respondents had physical health issues and 12.1% had some limitations in usual activities due to health problems [Table 4].
In our study population, 2.4% (1/41) and 7.3% (3/41) showed persistence of elevated C-reactive protein (CRP) and serum ferritin, respectively. Four (9.7%) patients had high D-dimer values (>1000 ng/mL). The laboratory parameters remained elevated for 7–9 weeks with a mean duration of 8 weeks. None of the HCWS presented with respiratory failure (pO2 <60 mmHg). Fifteen patients (5/41, 12.1%) were discharged with long-term oxygen therapy. The cases requiring oxygen therapy were on oxygen for 5–9 days postdischarge with a mean duration of 7 days.
Fatigue which was noticed in majority of patients required no specific treatment but were counseled and reassured. Recovery from fatigue was observed to occur over a course of 1–3 months. Uncontrolled diabetes mellitus was observed in 36.5% [Table 5]. Preexisting diabetes mellitus required insulin therapy for 3–4 weeks to control their high blood sugars. Respiratory involvement was seen in 17% of cases followed by cardiovascular system (14.6%) [Table 6]. According to WHO severity of corona disease, majority of cases 46.3% of cases of were moderate severity [Table 7]. Psychiatric manifestations were treated appropriately with medications based on the diagnosis and counseling.
Patients with aches and pains were counseled and were treated with tricyclic antidepressants with good outcomes and recovery observed over a period of 3–4 weeks.
Uncontrolled hypertension was treated with regular antihypertensives and beta-blockers with good control of blood pressure (BP).
Neurological deficits were found in four of the study group. One patient with a wrist drop underwent surgical intervention (with a diagnosis of the left ulnar neuropathy entrapment of elbow after nerve conduction study and ulnar nerve exploration and decompression was performed) and recovered satisfactorily. The other case of wrist drop was due to radial nerve compression. Another two patients had a history of partial foot drop (due to peroneal nerve compression) and recovered without any specific treatment. All four cases were evaluated with nerve conduction studies.
Paroxysmal sinus tachycardia and palpitations, with or without elevated BP had responded well to beta-blockers, without any adverse effects.
Late sequelae of COVID 19 infection have gained attention and generated interest recently. Several studies have reported persisting symptoms days to weeks after initial COVID illness. To adequately assess these persisting symptoms, there is a need to follow-up COVID-positive patients over a certain period to collect longitudinal data. Research in this context has provided some evidence of ongoing neurological symptoms beyond the acute phase of infection. The office for National Statistics, the UK-based survey, reported that among the 20,000 participants who were tested positive for COVID, 13.7% continued to experience symptoms for at least 12 weeks. A study conducted in the outpatient setting in Geneva on the persistence of symptoms concluded that 32% had symptoms on 30–45 days of COVID diagnosis. A case series which followed patients post-COVID hospitalization observed that 87.4% reported persisting symptoms 60 days postdischarge. COVID-19 recovered patients presented with several lingering manifestations pertaining to the respiratory, cardiac, cutaneous, and nervous systems. Persistence of nonspecific physical symptoms, which reflects the continuation of mild symptoms of acute illness is most commonly reported.[9–11] Of significance is dyspnea, fatigue, malaise, chest pain, and cough, which is similar to the findings in our study. Research has highlighted that increasing age has shown higher hospitalization rates and also advancing age increased the risk of long COVID. Non hospitalized patients aged above 50 years had higher prevalence of long COVID when compared to <35 years which reflects observations in our study. The presence of medical comorbidities also increases the chances of long COVID manifestations, with more the number of comorbidities greater being the risk irrespective of the age.
Investigations for abnormalities in inflammatory markers (e.g., CRP, ferritin, interleukin-6), lactate dehydrogenase, D-dimer, troponin, and creatine phosphokinase were observed in patients with persisting COVID symptoms. Few cases in our study had abnormalities in CRP, ferritin, and D-dimer, though not significant. The associations between the presence of laboratory abnormalities and the occurrence of long COVID-19 are not clearly established. In the current study, symptoms pertaining to the respiratory system were the most common presentation of the long haul COVID. Direct viral injury to epithelia, pulmonary thrombotic events, need for oxygen therapy, and ventilator support could be implicated in the emergence of the pulmonary sequelae. Postdischarge cardiopulmonary manifestations, such as dyspnea, palpitations, and chest pain, require careful consideration, especially in elderly patients with multiple comorbidities. The wide range of reported symptoms reflects the multi-organ involvement of COVID-19, mediated by direct tissue damage, hyperinflammation, and COVID-19-related coagulopathy.
Similar to follow-up, studies of 8–12 weeks of acute COVID-19 illness our study observed fatigue, weakness, and shortness of breath as the predominant sequelae.[15,16] Another prospective study of long-term consequences of acute COVID-19 infection at 6 months follow-up found similar symptoms as the most common presentation (fatigue/muscle weakness). There was no change in symptom profile observed in our study with the same initial symptoms reported by HCWS persisting until symptom resolution. The prolonged respiratory sequelae after recovery from COVID-19 appear to be the continuation of the respiratory symptoms present during acute infection.
Symptoms, such as visual disorders, hair loss, cutaneous, and deficits in hearing, were not reported in our study, although other studies have reported these manifestations. Rashes, urticarial eruptions, and squamous lesions. Other research in this field observed retinitis and optic neuritis in COVID survivors. Wrist drop and foot drop cases were reported post COVID in our study, but the association of these neurological sequelae directly to COVID cannot be established.
Moreover, in most cases, symptoms were not accompanied by blood test abnormalities, as values of lymphocyte count, D-dimer, and inflammatory markers results were in the normal range and abnormal results occurred in a minority of patients. In addition, several patients complained of additional symptoms, such as sleep difficulties, increased fear of getting reinfected with COVID-19, and decreased appetite. Although these symptoms are not life-threatening conditions, they can affect patients’ overall well-being and functional status and further lead to psychiatric consequences if left unattended. The highlight of our study is long-term follow-up of post-acute COVID consequences in HCWs. Our study has some limitations. This study reflects that the clinical manifestations of long COVID syndrome, though few investigations were ordered. Further information, which is needed to better characterize the burden and pathogenesis of possible chronic sequelae, should be obtained from future radiological and functional testing, including chest radiograph, spirometry, exercise testing, and echocardiography, in addition to other specialist evaluations, to be ordered on case-by-case basis.
Long COVID Syndrome is a complex and not yet fully understood condition. This study specifically aimed at evaluating long COVID symptoms in HCWS. Most of the HCWs had at least one lingering COVID symptoms lasting for 4 months post COVID, with symptoms continuing to persist up to 7 months after COVID infection. Respiratory and cardiovascular symptoms were the most common presentation. These symptoms noted in COVID-19 survivors improved over a period of time. We conclude that the treatment of acute COVID infection is not to be considered the end point-of-care, and there is a dire necessity to actively look for symptoms in the post-COVID cases.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
The authors would like to acknowledge the statistical services rendered by Mr. Janakiraman, Biostatistician of PESIMSR, Kuppam.
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