In this study, females were 50.3% of the population. The age distribution was asymmetric, however non-survivors belonged mainly to the elderly. The most prevalent comorbidities were hypertension, dyslipidaemia and BMI≥25Kg/m2. Clinical manifestations of SARS-CoV-2 pneumonia were fever and cough as the main symptoms, most of the patients had only 1-3 symptoms; this was especially clear in the elderly (≥75 years) whose clinical presentation was mainly with 1-3 symptoms. We described different characteristics between unilateral and bilateral pneumonia.
Some publications have been reporting age as a factor for developing severe illness due to SARS-CoV-2 infection (13), our study is consistent with this observation because elderly patients had more frequently bilateral pneumonia and also morbidity compared to younger patients.These findings are in concordance to Liu et al. who found more bilateral pneumonia in older patients (21). However, elderly presented fewer symptoms than those younger than 75 years because they used to have less pneumonia symptoms (22) and also their own comorbidities could overlap some COVID-19 symptoms. The comorbidities of our population (hypertension, dyslipidemia, diabetes and BMI≥25Kg/m2) were similar to the studies that have been published (13,17). These results are consistent with a meta-analysis published by Yang et al. (16), they found that patients infected by SARS-CoV-2 had hypertension (21.1%) and diabetes (9.7%) as the most prevalent comorbidities. Smoking was present in 7.5% of our population, less than others. Guan et al (6) reported 12.6% in smokers, that difference could be explained by incomplete EHR.
In this study, we described the symptoms and their chronology up until the appearance of pneumonia. We were interested in describing clinical patterns that could help us to decide when to request a chest X-ray and how to detect pneumonia. As expected, we found fever (83.8%), cough (81.5%), dyspnea (59.5%) and myalgia (30,1%) as the most frequent symptoms, consistent with the literature (9,12) and with Sun et al (23) who reported fever (89,1%) and cough (72.2%) as the most frequent symptoms; the differences among their percentages and ours could be explained by the accuracy in the EHR because the record was made daily.
We collected 12 symptoms, fever, cough and dyspnea were the most frequent, consistent with the meta-analysis of Rodriguez et al. who reported fever (88.7%, 95%CI 84.5–92.9%), cough (57.6%, 95%CI 40.8–74.4%) and dyspnea (45.6%, 95%CI 10.9–80.4%). We observed that most of the patients exhibited only 1-3 symptoms (56.1%). In our study the elderly had fewer symptoms, which is consistent with Niu et al. (24) who described less dyspnoea and cough in patients over 80 years however in their study fever (≥37,3ºC) was more prevalent than in our study (75% vs 69%); maybe this could be explained by the different age ranges (in their case: 50-64, 65-79 and ≥80 years).
In this study, the diagnosis of pneumonia was on day 7.8 of onset of the symptoms, similar to Wang et al. (25) where at hospital admission had a median on day 7.0 (IQR 4.0,8.0). These periods were longer than other publications which established the diagnosis through day 3.0 (IQR 1.0,6.0) for non-severe SARS-CoV-2 infection but on day 5.0 (IQR 2.0,7.0) in severe infections (6). Our study found that the diagnosis in the elderly group was made on day 6.7 of the onset. Furthermore, this group had more deaths (21%) and they were the ones who suffered more severe disease. They had tachypnoea, 92% of pulse oximetry, 43% of abnormal auscultation as well as more abnormalities in their blood tests. Most manuscripts published did not compare the differences across age groups because they were focused on severe and not severe cases. Niu et al. described 90.6% of oximetry and death in 18.8 of their ≥80 years patients which is similar to our results.
On another note, the physical examination was not recorded in all patients. At the moment, we still do not know the predictive values of symptoms and physical examination in COVID-19, especially of the lung auscultation which involves physical touch. In Spain, we suffered a shortage of personal protective equipment (PPE) for healthcare workers (40,921 of healthcare workers were infected by SARS-CoV-2 in the country till 11th of May (10) which made doctors cautious of examining the patients if they could get a diagnosis through anamnesis and chest X-ray. If we compare with other series, Guan et al. do not detail these physical signs in their data as well as Zhou et al. who just describe respiratory rate in 29% of their patients (26). A survey (27) was conducted in Canada to explore the opinions of GPs during the SARS (2003) and H1N1 (2010) outbreaks, GPs answered that they would avoid physical examinations in patients with SARS (62%) and patients with H1N1 (18%). More studies should be conducted to observe the benefit of the physical examination in the management of COVID-19. This should come along with qualitative research to understand the perspective of the doctors.
We described two clinical patterns by chest X-ray: unilateral and bilateral pneumonia however, little is known about other differences between both types of pneumonia (12). In this study, 73.3% of the types of pneumonia were bilateral; our results are in concordance with Shi et al. (n:416) (28) and Chen et al. (29), where around 75% of cases of pneumonia corresponded to bilateral and 25% to unilateral. Shi et al. as well as Guan et al. described bilateral pneumonia more frequently in severe cases. Unilateral pneumonia appeared more frequently in younger patients (53.7 vs 62.8 years), the onset was slightly later than bilateral pneumonia (8.9 vs 7.8 days) and most of them did not have red flags on their examination (abnormal auscultation, oximetry ≤ 94%) or blood tests ( CRP ≥ 81.5 mg/L, D-Dimer ≥ 520 μg/L, Lymphocytes ≤ 1,000 10e3/L, Fibrinogen ≥ 500 mg/dL) (6,28). They had higher oximetry (96% vs 94%) and more normal auscultation (34.8% vs 17.5%) without differences in other physical signs or symptoms. Unilateral pneumonia presented 37% of negative RT-PCR similar to Weissleder et al. who reported 30% ( range:10-40%) of false negative results (30). Any of our patients with unilateral pneumonia had a pulmonary embolism and just one of them did not survive.
Finally, health systems have faced significant stress because of pandemic, unfortunately more pandemic waves could happen till vaccination is available. This situation has highlighted the need for a whole patient perspective to take decisions especially when patients are assessed by remote consultation. Priority should be given to primary care who have a long-term relationship with their patients because not only they can follow them but they can manage those SARS-CoV-2 pneumonia patients without red flags in settings with access to laboratory tests and chest X-ray. We have found that unilateral pneumonia without red flags could be monitored closely in primary care without referring patients to the hospital if they can assure follow-up tightly. We hypothesise that unilateral SARS-CoV-2 pneumonia without red flags could be managed in primary care but more research is needed to characterise these clinical patterns related to the age and unilateral vs bilateral pneumonia.
Strengths and Limitations
To our knowledge, our study is the first one to describe patients with SARS-CoV-2 pneumonia diagnosed in a PCP. Besides, we described the clinical differences between bilateral and unilateral cases of pneumonia. However, limitations of this observational study should be addressed. Firstly, this study was carried out in a unique PCP, so the results might not be wildly generalisable. The cardiovascular factors could not be updated in the EHR (especially tobacco or BMI) but the comorbidities are usually updated because we have validated the diagnosis for research with success in other studies (31). In addition, a bias should be considered because we are located in a primary health centre which include a radiology department, so that we had facilities to diagnose SARS-CoV-2 pneumonia compared to other primary health centers of Madrid. Our study described the symptoms up through the onset of pneumonia but some of unilateral pneumonia should be addressed more thoroughly. On the one hand, we have not collected whether or not they could progress to bilateral pneumonia. On the other hand, we should approach differently those unilateral pneumonia with negative RT-PCR; we should have evidence if the RT-PCR was repeated several times. Further studies should be conducted to clarify these cases. Finally, we based our pneumonia diagnosis in the radiologist description but there could be an interpersonal variability in that description.