This cohort study followed up on COVID-19 patients to assess long-term symptoms that persist 90 days after the onset of the disease. Almost half of the sample was between 30 and 49 years old, and the majority were female. Multiple studies have found that COVID-19 is more prevalent in those between 30 and 60 years of age and in females 12,21,22.
One-third of the patients complain of dyspnea, fatigue, loss of taste or smell, and cough on day 10. These symptoms are commonly reported in different studies as a clinical manifestation of acute COVID-19 23–25. An online cross-sectional study in Saudi Arabia found that 73% of patients complained of fatigue and weakness 7-8.1 days after infection, and 66% had musculoskeletal pain, headache, loss of smell, cough, and loss of appetite 26. Following up with patients on Day 30, Day 60, and Day 90, dyspnea was the most commonly reported symptom, with one-fifth complaining of dyspnea after 90 days, followed by fatigue. Fatigue was the second most commonly reported symptom; the FAS scale revealed that 40% of patients have fatigue on day 30, one-third have it on day 60, and 15% have it on day 90. Patients reported headaches, loss of smell and taste, sleep disturbances, brain fog, and coughing by the end of day 90. These long symptoms align with findings from other studies evaluating long-COVID symptoms. Tabacof et al. found that within a year of infection, the most common persistent symptoms were fatigue (82%), brain fog (67%), and headache (60%) 18. Another Nigerian study found that two weeks after being released from isolation, more than one-third of patients had persistent fatigue (12.8%), headache (12.8%), and chest pain (9.8%) 22.
Although most COVID-19-infected patients recover within a few weeks after the acute infection, some continue to experience symptoms; approximately 40% of our patients had at least one symptom on Day 90. These results are consistent with the studies' findings to determine the rate of long-COVID symptoms. Moreno-Pérez et al. found that approximately 50% of patients had persistent symptoms 10–14 weeks after the first episode 27. Another study by Almasri et al. showed that 71.8% of patients still have one physical or psychological symptom three months or more after the first infection 28. A prospective cohort study for non-hospitalized COVID-19 patients observed that 27.8% have at least one symptom four months after the first symptom 4. A two-year prospective study in Germany found that 14.2% of patients reported post-COVID-19 symptoms 29. The differences in results could be attributed to the various types of studies used, the length of follow-up, and each country's healthcare system. However, because no particular test is used to confirm prolonged COVID-19 symptoms, these findings raise concerns among healthcare professionals about the full impact of COVID-19 on patients with unrelated symptoms.
Our findings revealed that older patients are nearly five times more likely than young patients to develop long-COVID symptoms, which could be attributed to the elderly's low immunity and comorbidities. Additionally, females are at higher risk of developing long-COVID symptoms than males. On the other hand, patients with comorbidities were more likely than those without comorbidities to develop long-COVID symptoms, but the difference was not significant at the multivariable level. The literature on the risk factors of long-COVID symptoms is still inconsistent. A prospective cohort study in Moscow found that females were twice as likely as males to have long-COVID symptoms and that having comorbidities was significantly associated with developing long-COVID symptoms 30. Another study in Jordan found that female patients, older patients, and patients with comorbidities had a significantly increased risk of developing long-COVID symptoms 28. On the other hand, a Nigerian study did not find an association between age, sex, presence of hypertension, diabetes, or multiple comorbidities and experiencing persistent symptoms post-COVID-19 infection 22. Hospitalization due to COVID-19 reflects the severity of the infection; our study revealed that hospitalized patients were five times more likely than outpatients to develop long-COVID symptoms. Different studies consider hospitalization as a significant risk factor to develope long-COVID symptoms. Pérez-González et al. demonstrated that hospitalized patients were more likely to have persistent symptoms than outpatients (52.3% vs. 38.2%) 31. In addition, Asadi-Pooya et al. found that the number of days spent in the hospital is significantly correlated with long-lasting covid symptoms three months after infection 32. These factors may exacerbate and prolong COVID-19 symptoms; therefore, HCWs should be aware of this vulnerable population, which may present with unrelated symptoms, delaying early diagnosis.
Patients with dyspnea on day 10 were at a nearly three-fold higher risk of developing long-COVID symptoms. This parameter mostly indicates lung involvement due to the infection, and the function of the respiratory system was affected and impaired. At the same time, we found a significant relationship between fatigue on day 60, with developing long-COVID symptoms. Fatigue is considered one of the most common persistent symptoms of patients with post-COVID-19 infection. It could be presented in young and older people. Although patients had no comorbidities, they might complain of fatigue. This supports Claudia Carvalho-Schneider et al.'s findings that early-stage infection-related dyspnea and persistent symptoms are related over time 25. Another study showed that 70% of COVID-19 hospitalized patients complained of fatigue and/or dyspnea seven months post-discharged 33.
Vaccination was reported among 41% of the sample; 76.6% of them were fully vaccinated. COVID-19 vaccination was found to be protective against developing long-COVID symptoms. Unvaccinated patients were seven times riskier of developing long-COVID symptoms than vaccinated patients. These findings support the evidence of the efficacy of COVID-19 vaccination. In a large UK study with 1.2 million participants, long-COVID symptoms were halved in vaccinated patients compared to unvaccinated patients 14. Another study revealed that vaccinated patients with two doses were 41% less frequently to have long-COVID symptoms than unvaccinated patients 15. These findings support the evidence of the vaccine's effectiveness in preventing the disease, limiting its spread, and mitigating its severity. They also emphasize the importance of promoting vaccination at the population level, given that vaccination uptake among the general population in Palestine by October 2022 was 36.6%, according to the Palestinian Corona Center 34.
One of the most important aspects of our study is that it is a prospective follow-up based on the WHO definition of long-COVID symptoms. Therefore, all patients continued the phone interview and answered all questions on days 10, 30, 60, and 90, and we were able to document and assess any new emerging symptoms. However, this study has some limitations that should be considered when interpreting the results. First, using self-reported data from telephone interviews rather than physical examinations or clinical investigations of patients may lead to information bias. Second, the study only included COVID-19 patients confirmed by PCR and not patients with symptoms or radiological signs of COVID-19, which could lead to selection bias; however, the fact that PCR was provided free of charge to all suspected COVID-19 cases in Palestine reduces this problem.