Immunological memory is formed for a pathogen when a person infected with it which leads to its imprint in the immune system. This immunological memory can protect that person from recurrent infection for decades. This is due to the formation of B and T lymphocytes with antigen-specific memory in addition to antibodies that protect against subsequent infections [22].
Viruses that cause systemic infections, such as rubella, mumps, measles, in addition to hepatitis A virus, is rare to cause re-infection. In contrast to this, viruses that cause mucosal infection without viremia, such as influenza, respiratory syncytial virus, and seasonal coronavirus, is common to recur [23]. This is explained by the much longer antibody response in systemic viral infections [24]. Recurrence of infection in respiratory viruses is caused either by weakened primary immune response such as in infection with respiratory syncytial virus, or exposure to genotype of another species (e.g., nasal viruses) or high diversity of viruses (e.g., flu viruses) [25].
Re-infection with COVID-19 has been reported worldwide [26]. Although zero conversion occurs in most of patients with SARS-COV-2 infection, the titer of binding and neutralizing antibodies varies between different patients and reduces with time [22]. Previous studies found that the more severe the disease the higher levels of neutralizing antibody titers formed and that these antibodies could be detected till 2–3 months after infection, in contrast to asymptomatic patients or patients with mild symptoms who had lower antibody titers that start to decline in less than 2 months from the beginning of the primary symptoms [27].
The antibodies titer required to neutralize the virus and to protect against recurrent infections should be known [28]. Researches done on SARS-CoV-2 and other coronaviruses reported that infection with coronaviruses can initiate long-term T-cell immunity which plays an important role in maintaining long-term immunity against viruses [21]. SARS-CoV-2-specific T, CD4 and CD8 cells reported in some studies to last more than 6 months after initial infection [24].
Susceptibility to re-infection depends on several factors that vary in different individuals including: the rate of antibody response and its durability as well as the duration of cellular immunity [25].
In our study we aimed at assessment of CT findings in patients with two episodes of infection with COVID-19 with more than 6 months gap between the two attacks to be sure that the level of neutralizing antibodies from the first episode has been decreased and the shedding of virus has stopped.
As regard the clinical assessment of the patients we reported that dyspnea was found in 80% of patients in the initial phase and decreased to 74% in the second phase. Other common symptoms were: fever and myalgia which presented by 100% of patients during the first infection but their frequency decreased to 96% in the re-infection.
Our reported data differed from what documented in another previous study in which the most common symptoms were headache (70.3%), loss of smell (70.2%), nasal obstruction (67.8%) and cough (63.2%) [29].
In another study that compared the symptoms experienced by patients re-infected with COVID between both infections, their results were similar to ours in the first attack of infection as they found that the most common symptoms were fever (63%) cough and dyspnea each was detected in (54%); moreover, they reported decrease in frequency of fever to 27% in the second episode, but they differed from us as they reported increased frequency of dyspnea to 72% in second episode [30].
As regard the radiological findings, no similar researches recorded and compared CT features in patients re-infected with COVID-19 since the beginning of world pandemic at December 2019 throughout first, second and third waves, most probably due to the previous thought that the immunity acquired through infection with COVID protects against re-infection. But with the progression of the pandemic and discovery of new strains of corona virus, as well as loss of the immunity acquired after first infection, the occurrence of re-infection become more common and reported.
We found two studies that compared CT findings of different patients between the first and second pandemic waves, one done in Ghana [31] and the other in Egypt [18]. In our study, we compared CT findings in the same patients that infected twice. The Egyptian study done by Samir et al. reported one case of COVID19 re-infection but they did not describe any details about his or her radiological findings in both attacks of infection.
In our research, we documented that the most common pattern of lung affection was ground glass opacification which was presented in (100%) of patients in both episodes. Bilateral lung affection was seen in 100% of patients in initial infection and decreased to 94% in re-infection. The most affected lobe is the lower lobe which detected in 98% in initial infection and in 100% of patients in re-infection.
This matched with what had been reported in the literature that the most typical pattern of COVID-19 pneumonia is ground glass opacification that was classically bilateral predominated in the peripheral and basal part of the lungs [12]. The frequent affection of lower lung zones is most probably due to the anatomy of the lower lung bronchus, which is short in length and thick, making the lower bronchus easy to be cached by the virus.
As regard the other less common radiological signs we detected that: Atoll sign seen in 64% of patients, Crazy paving seen in 70% of examined patients and nodule with ground glass halo presented in 42% of examined patients during the first attack, while in the re-infection the frequency of these signs was decreased.
Bull’s eye sign, architectural distortion and peri-lobular fibrosis are not detected in any of our patients initially. Peri-lobular fibrosis and architectural distortion develop late in the course of infection process and we assessed the patients in the acute phase. In the second phase, we detected bull's eye sign, architectural distortion and peri-lobular fibrosis in small percent of patients, the two later signs seen in the second phase may be due to sequel of the initial infection.
In the study done in Egypt [18], they reported some atypical CT findings which were only encountered during the second pandemic wave. They included the bronchiectatic changes, the “head-cheese” pattern, the “bulls-eye” sign and the cavitation.
As regard the severity of infection we used CT severity score, and we detected significant decrease in the CT severity score of the re-infected COVID-19 patients versus the initial COVID-19 infection. The decrease in CT severity score in most of patients in the recurrent infection is mostly due to the residual effect of the immune response developed after the initial infection which was not strong enough to prevent re-infection but it showed a role in decreasing disease severity.
In the Egyptian study [18], they reported 10% rise in the clinical and CT severity-score as well as the hospitalization rates in the second pandemic wave reported through the fourth and fifth decades of life.
We checked the relation between the radiological severity (assessed with CT severity score) and clinical severity expressed by suffering from respiratory distress and reduction of O2 saturation, and we reported a statistically significant relation between CT severity score and the presence of respiratory distress as well as reduction in O2 saturation in both episodes of infection.
This matched with the result of study done by Saeed et al. [32], who found that oxygen requirements increase with the increasing CT severity.
The main limitations to our study were small sample size, lack of availability of the genetic study which allows the comparison between the virus strains between the two episodes, as well as lack of other similar researches to be compared with our study.
